Gatifloxacin

Elucidation of Inhibitory Activities Against Bacterial DNA Gyrase

Studies have determined the inhibitory activities of this compound against bacterial DNA gyrase. For instance, this compound demonstrated potent inhibitory activity against Escherichia coli DNA gyrase with a 50% inhibitory concentration (IC50) of 0.109 μg/ml. nih.govasm.orgnih.govmedchemexpress.com This highlights its effectiveness in inhibiting this essential bacterial enzyme.

Comparative Selectivity for Bacterial DNA Gyrase versus Mammalian Topoisomerase II

This compound exhibits a high selectivity for bacterial type II topoisomerases compared to mammalian topoisomerase II. nih.govasm.orgnih.gov The IC50 of this compound for HeLa cell topoisomerase II was significantly higher (265 μg/ml) than its IC50 values for bacterial enzymes like S. aureus topoisomerase IV (13.8 μg/ml) and E. coli DNA gyrase (0.109 μg/ml). nih.govasm.orgnih.govmedchemexpress.com The ratio of the IC50 for HeLa cell topoisomerase II to that for bacterial enzymes was more than 2,400 times higher, indicating a substantially greater selectivity for bacterial targets. nih.govasm.orgnih.gov This differential activity is a key factor in the drug's ability to target bacterial cells with less impact on host cells.

Here is a table summarizing the inhibitory activities:

Molecular Interaction with GyrA Subunit and Bacterial DNA

This compound targets the A subunit of DNA gyrase. patsnap.compatsnap.com By binding to the GyrA subunit, this compound inhibits the enzyme's ability to re-ligate cleaved DNA strands. patsnap.compatsnap.com This interaction stabilizes the transient double-strand breaks introduced by DNA gyrase, leading to the accumulation of double-stranded breaks in the bacterial chromosome. patsnap.com Fluoroquinolones, including this compound, poison cells by trapping DNA gyrase and topoisomerase IV on chromosomes as quinolone-enzyme-DNA complexes. nih.gov These complexes block the movement of replication forks and transcription complexes. researchgate.net Fluoroquinolones bind to a region near tyrosine-122 in the N-terminal domain of the GyrA subunits, forming a ternary complex that blocks movement over the replication fork. mdpi.com

Allele-Specific Enhancement of Inhibition Against Resistant Gyrase Mutants

The C-8-methoxy group of this compound contributes to enhanced activity against resistant gyrase mutants. nih.govasm.org Studies using isogenic sets of quinolone-resistant gyrA mutants of Escherichia coli have shown that the C-8-methoxy group lowered the resistance due to mutations, particularly those mapping in α-helix 4 of the GyrA subunit, which is thought to interact with DNA. nih.govasm.org This suggests that the C-8-methoxy group facilitates the attack of this compound on these resistant gyrase variants. nih.gov

Influence of the C-8 Methoxy Group on DNA Gyrase Inhibition

The presence of a methoxy group at the C-8 position of the quinolone ring in this compound is associated with enhanced inhibitory activity against bacterial DNA gyrase. researchgate.netoup.comnih.govnih.gov This structural feature appears to contribute to increased potency against Gram-positive bacteria and improved activity against DNA gyrase mutants. oup.comresearchgate.net Studies comparing this compound (C-8-methoxy) with compounds lacking this group (C-8-H), such as ciprofloxacin and AM1121, have shown that the C-8-methoxy compounds exhibit higher inhibitory activity against DNA gyrase. nih.govnih.gov Specifically, the inhibitory activities of C-8-methoxy compounds against DNA gyrase were approximately six times higher than those of their C-8-H counterparts in Staphylococcus aureus. nih.gov This enhancement of DNA gyrase inhibition is considered a possible mechanism underlying the potent antibacterial activity of this compound. nih.gov

In Silico Modeling and Docking Studies of this compound-DNA Gyrase Complexes

In silico studies, including molecular modeling and docking, have been conducted to investigate the interaction between this compound and bacterial DNA gyrase. These studies aim to understand the binding modes and affinities of this compound with the enzyme. academicjournals.orgacademicjournals.orgresearchgate.nettandfonline.com Docking calculations have been used to predict the interaction between this compound and the "Quinolone Resistance Determining Region" (QRDR) of E. coli DNA Gyrase-A. researchgate.netitmedicalteam.pl These studies can help identify critical amino acid residues involved in the binding of quinolones to DNA gyrase, such as Asp87, Thr88, Arg91, and Met92 in E. coli. jppres.com Molecular modeling has also been used to elucidate the hypothetical structures of enzymes like Mycobacterium tuberculosis DNA gyrase and investigate the binding affinities of this compound analogs. tandfonline.com These computational approaches provide valuable insights into the molecular basis of this compound's interaction with its target enzyme.

Elucidation of Inhibitory Activities Against Bacterial Topoisomerase IV

Research has elucidated the inhibitory activities of this compound against bacterial type II topoisomerases, including topoisomerase IV. Studies comparing this compound with other quinolones have shown its potent inhibitory effects on bacterial topoisomerase IV. nih.gov this compound binds to the B subunit of topoisomerase IV, preventing its ability to relax supercoiled DNA and decatenate chromosomes. patsnap.com The inhibitory activities of quinolones against bacterial type II topoisomerases, such as Staphylococcus aureus topoisomerase IV and Escherichia coli DNA gyrase, have been shown to correlate significantly with their antibacterial activities. nih.gov

Comparative Inhibition of Topoisomerase IV Across Diverse Bacterial Species

This compound demonstrates inhibitory activity against topoisomerase IV in a range of bacterial species. While fluoroquinolones generally target DNA gyrase as the primary target in Gram-negative bacteria and topoisomerase IV in Gram-positive bacteria, the specific preference can vary depending on the quinolone and bacterial species. asm.orgoup.com For instance, while some compounds like this compound target gyrase in Streptococcus pneumoniae, they appear to target topoisomerase IV in Staphylococcus aureus. asm.org Studies have shown this compound to be highly active against various bacterial species, including Staphylococcus aureus and Escherichia coli, with demonstrated minimum inhibitory concentrations (MICs). ontosight.aipsu.edu

Data illustrating the comparative inhibitory activities of this compound against topoisomerase IV in different bacterial species, often measured by IC50 (50% inhibitory concentration) values, highlights its potency. For example, this compound has shown potent inhibitory activity against S. aureus topoisomerase IV. nih.gov

Note: While the table includes DNA Gyrase data for comparison as per the source, the focus remains on Topoisomerase IV inhibition.

The Dual-Targeting Strategy in Fluoroquinolones and this compound's Role

Fluoroquinolones, including this compound, employ a dual-targeting strategy, inhibiting both bacterial DNA gyrase and topoisomerase IV. patsnap.comnih.govwikipedia.orgwikidata.orgontosight.ai This dual action is crucial for their broad-spectrum activity and helps mitigate the development of bacterial resistance. patsnap.comdovepress.com DNA gyrase is primarily involved in introducing negative supercoils into DNA, essential for replication and transcription, while topoisomerase IV is key for chromosome segregation during cell division. patsnap.compatsnap.compatsnap.com By inhibiting both enzymes, this compound effectively disrupts critical DNA processes. patsnap.compatsnap.compatsnap.comnih.gov this compound binds to specific subunits of these enzymes – the A subunit of DNA gyrase and the B subunit of topoisomerase IV – preventing the religation of cleaved DNA strands. patsnap.compatsnap.com This dual targeting reduces the likelihood of resistance developing through a single mutation in either target enzyme, as concomitant mutations in both genes would be required. dovepress.com

Staphylococcus Species: Methicillin-Susceptible and Coagulase-Negative Staphylococci

This compound is highly active against methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-susceptible coagulase-negative staphylococci. oup.comnih.govpsu.edutandfonline.com Studies have shown this compound to be more potent than ciprofloxacin and ofloxacin against MSSA and methicillin-susceptible Staphylococcus epidermidis, Staphylococcus haemolyticus, and Staphylococcus saprophyticus. oup.com Modal MIC90 values for this compound against these methicillin-susceptible strains were typically low, often around 0.12 mg/L. oup.com

Against methicillin-resistant Staphylococcus aureus (MRSA), the potency of quinolones, including this compound, is significantly reduced, with MIC90 values increasing substantially compared to susceptible strains. oup.comtandfonline.com this compound demonstrated moderate activity against MRSA, inhibiting a percentage of strains at its susceptibility breakpoint. nih.gov Similarly, the susceptibility of coagulase-negative staphylococci to this compound can be variable, with higher MIC90 values observed for strains resistant to methicillin and/or ciprofloxacin. tandfonline.com

Table 1: In Vitro Activity of this compound Against Staphylococcus Species

Note: MIC90 values may vary depending on the specific study, isolate source, and testing methodology.

Streptococcus Species: Streptococcus pneumoniae (including penicillin non-susceptible strains) and Viridans Group Streptococci

This compound is highly active against Streptococcus pneumoniae, including strains with reduced susceptibility or resistance to penicillin. oup.comnih.govoup.comnih.govnih.govasm.orgnih.govscielo.broup.comnih.gov Its activity against pneumococci is generally comparable to or better than that of older fluoroquinolones like ciprofloxacin and ofloxacin. oup.comupmc.comnih.govoup.com The MIC90 for this compound against S. pneumoniae is consistently low, reported around 0.5 mg/L, regardless of penicillin susceptibility. oup.comnih.govnih.govasm.orgnih.govoup.com Studies have shown this compound to be the most active agent tested against streptococci, including penicillin-nonsusceptible S. pneumoniae. nih.gov

Against Viridans group streptococci, this compound also demonstrates good activity. nih.govnih.govpsu.edu MIC90 values for this compound against Viridans group streptococci have been reported at ≤ 1.0 mg/L and 0.5 mg/mL, comparable to imipenem. nih.govnih.gov

Table 2: In Vitro Activity of this compound Against Streptococcus Species

Note: MIC90 values may vary depending on the specific study, isolate source, and testing methodology.

Enterococcus Species: Enterococcus faecalis and Enterococcus faecium

This compound shows activity against Enterococcus species, including Enterococcus faecalis and some strains of Enterococcus faecium. oup.comoup.comnih.govoup.com Its potency against enterococci is generally considered moderate compared to its activity against staphylococci and streptococci. nih.gov

Against Enterococcus faecalis, this compound has demonstrated activity with reported MIC50 and MIC90 values of 0.5 and 1 mg/L, respectively. oup.comoup.com Some studies indicate that this compound was more active than other quinolones against Enterococcus faecalis. oup.comoup.com Against Enterococcus faecium, this compound is less potent than against E. faecalis, with a reported MIC90 of 4 mg/L against some strains. oup.comoup.com Resistance to this compound has been observed in some E. faecalis isolates, particularly uropathogenic strains, with high MIC90 values reported in some studies. oup.cominternationalscholarsjournals.com All five fluoroquinolones tested in one study, including this compound, had poor activity against Enterococcus faecium. jmilabs.com

Table 3: In Vitro Activity of this compound Against Enterococcus Species

Note: MIC values may vary depending on the specific study, isolate source, and testing methodology.

Other Gram-Positive Organisms: Aerococcus, Listeria monocytogenes, Micrococcus, Stomatococcus mucilaginous, Bacillus, and Rhodococcus equi

This compound has demonstrated activity against a range of other Gram-positive organisms. nih.govpsu.eduscilit.com It has been shown to inhibit all tested isolates of Aerococcus, Listeria monocytogenes, Micrococcus, Stomatococcus mucilaginous, Bacillus, and Rhodococcus equi at low concentrations (≤ 2 mg/L). nih.govpsu.edu this compound was reported as the most potent agent against Listeria monocytogenes compared to other tested agents in one study. oup.com

Enterobacteriaceae: Escherichia coli, Klebsiella pneumoniae, Enterobacter aerogenes

This compound is active against many members of the Enterobacteriaceae family, including Escherichia coli, Klebsiella species, and Enterobacter species. oup.comnih.govoup.comoup.comnih.govnih.govpsu.edutandfonline.comoup.comnih.gov Against most Enterobacteriaceae, this compound MIC90s typically range from 0.06 to 0.5 mg/L. oup.com

For Escherichia coli, this compound demonstrates good activity. oup.comoup.comnih.govpsu.edunih.gov While ciprofloxacin was often more potent against E. coli, this compound inhibited a high percentage of isolates at low concentrations (≤ 1 mg/L). nih.gov MIC90 values for E. coli have been reported at ≤ 0.39 mg/L and ≤ 0.5 mg/mL. oup.comoup.comnih.gov Against ciprofloxacin-resistant E. coli, this compound showed some reduced susceptibility but may still be useful. researchgate.netnih.gov

This compound is also active against Klebsiella pneumoniae. oup.comoup.comnih.govpsu.edunih.gov MIC90 values for K. pneumoniae have been reported at ≤ 0.39 mg/L, ≤ 0.5 µg/ml, and 0.78 mg/L. oup.comoup.comtandfonline.com

Against Enterobacter aerogenes, this compound has shown activity. psu.edunih.gov MIC90 values for Enterobacter aerogenes were reported to be one fourth to one fifth the values for moxifloxacin in one study. nih.govresearchgate.net

Table 4: In Vitro Activity of this compound Against Select Enterobacteriaceae

Note: MIC90 values may vary depending on the specific study, isolate source, and testing methodology.

Pseudomonas Species: Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas stutzeri

This compound exhibits activity against Pseudomonas species, although its potency compared to other fluoroquinolones like ciprofloxacin can vary. Against Pseudomonas aeruginosa, this compound and ofloxacin have shown similar anti-pseudomonal potency, while ciprofloxacin has demonstrated two- to eight-fold greater potency in some studies. nih.govoup.com MIC90 values for P. aeruginosa have been reported around 4 mg/L for this compound and ofloxacin, while ciprofloxacin MIC90s were lower. oup.com In one study, intermediate susceptibility (MIC of 4 µg/ml) to this compound was noted in one isolate of P. aeruginosa. nih.gov

For Pseudomonas fluorescens and Pseudomonas stutzeri, this compound MIC90s were reported as 8 mg/L and 0.25 mg/L, respectively, which were the same as ofloxacin MIC90s. oup.com Ciprofloxacin MIC90s were four- to eight-fold lower against these species. oup.com

Synergistic killing effects have been observed with this compound in combination with other antimicrobial agents against P. aeruginosa and P. stutzeri. For P. aeruginosa, combinations with imipenem, aztreonam, or piperacillin were most often synergistic. nih.gov Against P. stutzeri, synergism was noted with combinations including aztreonam, piperacillin, or amikacin. nih.gov

Haemophilus influenzae and Moraxella catarrhalis

This compound is highly potent against Haemophilus influenzae and Moraxella catarrhalis. nih.govtandfonline.comscielo.br Studies have reported very low MIC50 and MIC90 values for this compound against these pathogens, often ≤0.03 µg/ml. nih.gov this compound has been described as one of the most active agents tested against H. influenzae. nih.gov Compared to other fluoroquinolones, this compound's activity against H. influenzae and M. catarrhalis is excellent, with MIC90 values significantly lower than susceptibility breakpoints. nih.govuwi.edu

Neisseria gonorrhoeae

This compound demonstrates exquisite potency against Neisseria gonorrhoeae, with reported MIC90 values as low as 0.016–0.25 mg/L. tandfonline.comoup.com

Acinetobacter Species: Acinetobacter lwoffi, Acinetobacter baumanii

This compound shows good potency against Acinetobacter species. oup.comscielo.br Specifically, it has been reported to be very active against Acinetobacter lwoffi, with a MIC100 of 0.12 mg/L in one study. karger.comnih.gov Moderate activity has been observed against Acinetobacter baumanii. karger.comnih.gov MIC90 values for Acinetobacter species have ranged from 0.5 to 1 mg/L. oup.com While this compound has activity, some studies indicate that Acinetobacter species can be less susceptible to fluoroquinolones, including this compound, compared to other Gram-negative organisms. tandfonline.comkarger.comnih.govdoi.org

Stenotrophomonas maltophilia and Burkholderia cepacia

The activity of this compound against Stenotrophomonas maltophilia and Burkholderia cepacia can be variable. This compound has shown greater potency against S. maltophilia compared to ciprofloxacin or ofloxacin. oup.comnih.gov MIC50 and MIC90 values for this compound against S. maltophilia have been reported as 1 and 4 mg/L, respectively, in one study, and 0.5 and 12 µg/mL in another. oup.commdpi.com Susceptibility rates of S. maltophilia to this compound have been reported around 71%. nih.govresearchgate.netasm.org Time-kill studies have indicated that this compound can be bactericidal against S. maltophilia at concentrations equivalent to twice or four times the MIC. nih.govasm.org

Against Burkholderia cepacia, this compound and ciprofloxacin have shown comparable, though often poor, potencies, with MIC50s and MIC90s around 4 and 8 mg/L. oup.comoup.com All three quinolones (this compound, ciprofloxacin, and ofloxacin) have been reported as equipotent against B. cepacia with MIC90s of 8 mg/L. nih.gov However, some studies indicate that susceptibility of Burkholderia species to this compound can be lower compared to other agents like trimethoprim/sulfamethoxazole or meropenem. scielo.brresearchgate.net Synergistic killing against B. cepacia strains has been observed with this compound in combination with ceftazidime or aztreonam, even in strains non-susceptible to one of the agents. nih.gov

Alcaligenes xylosoxidans

Alcaligenes xylosoxidans strains have been reported as relatively resistant to this compound and other tested quinolones. karger.comnih.gov However, earlier studies indicated that this compound had good potency against Alcaligenes species, with MIC90s around 1 mg/L. oup.comoup.com

Mycobacteria: Mycobacterium tuberculosis, Mycobacterium fortuitum Group, Mycobacterium chelonae, Mycobacterium avium-intracellulare

This compound has shown activity against certain mycobacteria. It has been reported to be more potent against Mycobacterium tuberculosis compared to ciprofloxacin and ofloxacin, with an MIC90 of 0.25 mg/L. oup.com Studies evaluating the activity against rapidly growing mycobacteria (RGM) found that this compound inhibited 90% of Mycobacterium fortuitum group isolates at ≤0.12 μg/ml and 90% of Mycobacterium chelonae isolates at ≤4 μg/ml. nih.govasm.orgnih.gov this compound was generally fourfold more active than ciprofloxacin against these RGM. nih.govasm.org For the M. fortuitum group, 100% of isolates tested in one study were susceptible to this compound at MICs of ≤0.5 μg/ml. asm.org Against M. chelonae isolates, 97% were susceptible or intermediate to this compound at an MIC of ≤4 μg/ml in one study. asm.org However, some studies on isolates from specific geographic areas, such as Brazil, have indicated that many M. chelonae and M. abscessus isolates from infectious keratitis were resistant to fluoroquinolones, including this compound, with MIC90s greater than 32 μg/mL.

This compound demonstrated poor potency against Mycobacterium avium-intracellulare compared to M. tuberculosis, although it was still more active than comparator quinolones like ciprofloxacin and ofloxacin against M. avium-intracellulare strains. oup.comoup.com In one study, the in vitro activity of this compound against M. avium was found to be less than that of sitafloxacin and moxifloxacin based on MICs, MBCs, and MPCs. nih.gov

Table 1: In Vitro Activity of this compound Against Select Mycobacteria

Note: MIC values can vary depending on the study methodology and the specific isolates tested.

Mycoplasma Species and Chlamydia Species

This compound has demonstrated good in vitro activity against Mycoplasma species and Chlamydia species. oup.comasm.org It has shown at least eight-fold better anti-chlamydial and anti-mycoplasma potency compared to ciprofloxacin and ofloxacin. oup.comoup.com The MIC90 for Mycoplasma species was reported as 0.13 mg/L. oup.com Specifically, this compound was 10-fold more potent than ciprofloxacin and ofloxacin against Mycoplasma pneumoniae and eight- to 16-fold more potent against Mycoplasma hominis based on MIC50 values. oup.comoup.com The MICs of this compound for Mycoplasma were ≤0.25 mg/L. oup.comoup.com

Against Chlamydia trachomatis and Chlamydia pneumoniae, this compound was highly potent, being eight- to 16-fold more potent than ofloxacin and ciprofloxacin. oup.comoup.com The MIC90 for Chlamydia pneumoniae was reported as 0.125 mg/L. nih.gov One study found this compound to be slightly less active against C. trachomatis and slightly more active against C. pneumoniae than ofloxacin, with MICs at which 90% of isolates had no inclusions of 0.25 mg/L. oup.comnih.gov

Table 2: In Vitro Activity of this compound Against Mycoplasma and Chlamydia Species

Obligate Anaerobes: Bacteroides fragilis, Clostridium difficile, Fusobacterium spp., Prevotella spp., Porphyromonas spp., Peptostreptococci

This compound has demonstrated activity against obligate anaerobic bacteria. oup.comasm.org Unlike some other quinolones like ciprofloxacin and ofloxacin, this compound has shown activity against Bacteroides fragilis and Clostridium difficile. oup.comoup.com

In a study comparing this compound to other quinolones and antimicrobials against 294 anaerobes, the this compound MICs for 50% and 90% of the isolates tested were 0.5 and 2 mg/liter, respectively. asm.orgnih.gov These values were significantly lower than those for ciprofloxacin. asm.orgnih.gov this compound was found to be active against Bacteroides tectum, Prevotella spp., Porphyromonas spp., and peptostreptococci. asm.orgnih.gov However, Fusobacterium species were sometimes resistant. asm.orgnih.gov With the exception of some Fusobacterium varium isolates (MICs, 2–4 mg/L), this compound MICs were ≤0.5 mg/L for other Fusobacterium spp. oup.com

Table 3: In Vitro Activity of this compound Against Select Obligate Anaerobes

Note: The MIC90 > 8 mg/L for comparator quinolones highlights this compound's activity against these organisms where others were less effective. The exact MIC90 for this compound against these specific species was not explicitly provided in the snippets, but its activity was noted.

Periodontopathic Bacteria: Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia

This compound has shown potential antibacterial effects on periodontopathic bacteria. scirp.orgscirp.orgresearchgate.netresearchgate.netscirp.orgcqvip.com Studies have investigated its activity against Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Prevotella intermedia. scirp.orgresearchgate.netscirp.org

This compound inhibited the growth of these periodontopathic bacteria in broth. scirp.org The minimum inhibitory concentration (MIC) for A. actinomycetemcomitans was found to be as low as 2.5 nM. scirp.org For P. gingivalis, an MIC of 50 nM was reported in a study focusing on canine periodontopathic bacteria, including Porphyromonas gulae. scirp.orgresearchgate.net this compound also exhibited antibacterial effects on P. intermedia at concentrations such as 7.5 × 102 nM. scirp.org this compound has demonstrated bactericidal effects on these tested bacteria in a concentration-dependent manner. scirp.orgscirp.org

Table 4: In Vitro Activity of this compound Against Select Periodontopathic Bacteria

Ralstonia solanacearum, Pseudomonas syringae, Xanthomonas campestris pv. vesicatoria

This compound hydrochloride has shown significant inhibitory effects against key phytopathogens such as Ralstonia solanacearum, Pseudomonas syringae pv. tomato DC3000, and Xanthomonas campestris pv. vesicatoria. nih.govfrontiersin.orgresearchgate.netfrontiersin.org

Against R. solanacearum, this compound hydrochloride exhibited a high inhibitory effect, with a reported inhibition rate of 95% at a concentration of 0.0625 mg/L. nih.govfrontiersin.orgresearchgate.net The minimum inhibitory concentration (MIC) for R. solanacearum was determined to be 0.125 mg/L. nih.govfrontiersin.orgresearchgate.net Treatment with 0.5 mg/L of this compound hydrochloride was effective in killing more than 95% of R. solanacearum bacteria. nih.govfrontiersin.orgresearchgate.net

This compound hydrochloride also demonstrated good antibacterial activity against Pseudomonas syringae pv. tomato DC3000 and Xanthomonas campestris pv. vesicatoria. nih.govfrontiersin.orgresearchgate.netfrontiersin.org At a concentration of 0.5 mg/L, this compound hydrochloride substantially inhibited the growth of both P. syringae and X. campestris pv. vesicatoria in liquid culture. frontiersin.org Higher concentrations showed bactericidal activity; 1 mg/L killed 98% of P. syringae, and 4 mg/L killed approximately 90% of X. campestris pv. vesicatoria. frontiersin.orgfrontiersin.org

Table 5: Activity of this compound Hydrochloride Against Select Phytopathogenic Bacteria

Inhibition of Biofilm Production in Plant Pathogens

This compound hydrochloride has been shown to significantly inhibit biofilm formation by Ralstonia solanacearum. nih.govfrontiersin.orgresearchgate.net This inhibitory effect on biofilm production represents an additional mechanism of action against this important plant pathogen. nih.govfrontiersin.orgresearchgate.net

Comparison with Other Fluoroquinolones (e.g., Ciprofloxacin, Levofloxacin, Moxifloxacin, Ofloxacin, Trovafloxacin, Sparfloxacin)

Comparative in vitro studies have evaluated the activity of this compound alongside other fluoroquinolones such as ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin, trovafloxacin, and sparfloxacin. These studies often assess the minimum inhibitory concentrations (MICs) of the antibiotics against various bacterial isolates to determine their relative potency.

Research indicates that this compound generally exhibits potent activity against a broad spectrum of bacteria, including many Gram-positive and Gram-negative pathogens. Comparisons with other fluoroquinolones reveal variations in activity depending on the specific bacterial species and the resistance profiles of the isolates tested. For instance, some studies may show this compound having comparable or even superior activity against certain Gram-positive cocci, including Streptococcus pneumoniae, compared to some earlier generation fluoroquinolones like ciprofloxacin or ofloxacin. Newer fluoroquinolones like moxifloxacin may demonstrate similar or enhanced activity against certain Gram-positive bacteria compared to this compound in some studies.

Against Gram-negative bacteria, this compound typically shows good activity, comparable to or slightly less potent than ciprofloxacin against some species like Pseudomonas aeruginosa. The activity against Enterobacteriaceae is generally strong among the tested fluoroquinolones, with variations in specific MIC values observed across different studies and bacterial strains.

Trovafloxacin, another fourth-generation fluoroquinolone, was noted to have better Gram-positive bacterial coverage but less Gram-negative coverage than previous fluoroquinolones; however, its use was limited due to hepatotoxicity concerns. wikipedia.orglabshare.cn Sparfloxacin, a third-generation fluoroquinolone, has also been compared to this compound in terms of in vitro activity, with studies assessing their effectiveness against various respiratory and other pathogens. wikipedia.orgtruemeds.in

Due to the extensive nature of comparative in vitro studies across numerous bacterial species and diverse collections of isolates, presenting a single comprehensive data table is challenging. However, representative findings from various studies often highlight the following trends in MIC values (lower MIC indicates higher potency):

Note: This table provides illustrative MIC ranges based on general trends observed in various studies and should not be considered exhaustive or definitive for all isolates.

Comparison with Beta-Lactam Antibiotics (e.g., Cefepime, Meropenem, Piperacillin/Tazobactam, Amoxicillin/Clavulanate)

Comparisons between this compound and beta-lactam antibiotics, such as cefepime, meropenem, piperacillin/tazobactam, and amoxicillin/clavulanate, demonstrate differences in their spectrum of activity. Beta-lactams primarily target bacterial cell wall synthesis by inhibiting penicillin-binding proteins (PBPs). mims.commims.com

This compound, by inhibiting DNA gyrase and topoisomerase IV, offers activity against some bacteria that may be resistant to beta-lactams due to mechanisms like beta-lactamase production. labshare.cn

Studies comparing this compound to extended-spectrum cephalosporins like cefepime show varying results depending on the bacterial species. Cefepime is a fourth-generation cephalosporin with broad activity against both Gram-positive and Gram-negative bacteria, including Pseudomonas aeruginosa. wikipedia.orgfishersci.cacalpaclab.com Meropenem, a carbapenem, is known for its very broad spectrum of activity, often considered a drug of last resort for serious infections. mims.comwikipedia.orgwikidoc.orgnih.gov Piperacillin/tazobactam, a combination of an extended-spectrum penicillin and a beta-lactamase inhibitor, has potent activity against many Gram-negative bacteria, including P. aeruginosa, and good activity against some Gram-positive and anaerobic bacteria. mims.comwikipedia.orgfishersci.cauni.lu Amoxicillin/clavulanate is active against a range of Gram-positive and Gram-negative bacteria, including beta-lactamase-producing strains.

In vitro data suggest that this compound can be active against some isolates resistant to these beta-lactams. Conversely, beta-lactams, particularly carbapenems like meropenem, may show broader or more potent activity against certain bacterial groups compared to this compound. Synergy studies combining trovafloxacin (another fluoroquinolone) with beta-lactams and aminoglycosides have indicated that synergy is strain-specific and not commonly encountered. labshare.cn While this specific finding is for trovafloxacin, it highlights that simple additive or synergistic effects are not guaranteed when combining fluoroquinolones with beta-lactams.

Comparison with Aminoglycosides (e.g., Gentamicin)

Aminoglycosides like gentamicin exert their antibacterial effect by inhibiting bacterial protein synthesis. Comparisons with this compound, which targets DNA synthesis, reveal distinct mechanisms of action. wikipedia.org

In vitro studies comparing this compound and gentamicin show differences in their activity against various bacterial species. Gentamicin is typically very active against many Gram-negative bacteria, including Pseudomonas aeruginosa, but has limited activity against anaerobic bacteria and most Gram-positive bacteria when used alone. This compound, with its broader spectrum, is active against both Gram-positive and Gram-negative pathogens.

As mentioned previously, synergy studies involving trovafloxacin and aminoglycosides indicate that synergy is strain-specific. labshare.cn This suggests that while combinations might be used clinically in certain situations, the in vitro interaction between this compound and aminoglycosides would also likely be complex and dependent on the specific bacterial isolate.

Comparison with Other Antimicrobial Classes (e.g., Metronidazole, Clindamycin, Erythromycin)

This compound has also been compared in vitro to antibiotics from other classes, such as metronidazole, clindamycin, and erythromycin, which have different mechanisms of action and spectra.

Metronidazole is primarily active against anaerobic bacteria and certain protozoa. wikipedia.orgwikidata.orgmims.comfishersci.dkfishersci.ca Its mechanism involves the production of reactive nitrogen species that damage microbial DNA. This compound generally has good activity against many anaerobic bacteria, overlapping with metronidazole's spectrum in this regard, but this compound also covers a wide range of aerobic Gram-positive and Gram-negative bacteria that metronidazole does not.

Clindamycin is a lincosamide antibiotic that inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit. It is primarily active against Gram-positive bacteria, including many staphylococci and streptococci, and a wide range of anaerobic bacteria. Erythromycin is a macrolide antibiotic that also inhibits protein synthesis by binding to the 50S ribosomal subunit. It is primarily active against Gram-positive bacteria and some atypical pathogens.

In comparisons with clindamycin and erythromycin, this compound often demonstrates a broader spectrum of activity, particularly against Gram-negative aerobic bacteria. While clindamycin and erythromycin are valuable for specific infections, this compound's dual targeting of DNA gyrase and topoisomerase IV provides coverage against a wider array of pathogens, including many that may be resistant to macrolides or lincosamides.

This comparative analysis highlights that this compound possesses a broad in vitro antimicrobial spectrum, often demonstrating potent activity against pathogens susceptible to other fluoroquinolones, and providing coverage against some bacteria resistant to beta-lactams, aminoglycosides, and certain other classes of antibiotics.

Predicting Binding Modes and Affinities with Target Proteins

Molecular docking simulations are employed to predict the preferred orientation (binding mode) of this compound within the active site of target proteins and to estimate the strength of the interaction (binding affinity). Studies have investigated the binding of this compound and its derivatives to various proteins, including bacterial enzymes like DNA gyrase and topoisomerase IV, as well as other potential targets such as estrogen receptor β and pancreatic α-amylase. nih.govkaznu.kzglobalresearchonline.net

For instance, molecular docking studies assessing this compound derivatives as potential antidepressant agents evaluated their binding affinities to protein 8FSB. This compound itself showed a binding energy of -6.9 kcal/mol with protein 8FSB. researchgate.netbiotech-asia.orgresearchgate.net Its derivatives demonstrated higher binding affinities, ranging from -7.9 to -11.4 kcal/mol. researchgate.netbiotech-asia.orgresearchgate.net Another study investigating potential antimycobacterial activity docked quinolinone-based thiosemicarbazones, including compounds structurally related to quinolones, against targets like DNA gyrase, enoyl-acyl carrier protein reductase (InhA), and decaprenylphosphoryl-β-D-ribose-2'-oxidase (DprE1). nih.gov The binding affinity was assessed using Vina scores, where lower values indicate stronger binding. nih.gov

In the context of periodontal therapy, computational studies explored the binding affinity of this compound and other fluoroquinolones with estrogen receptor β (PDB 1QKM) and Gingipain K (PDB 6I9A). This compound showed significant binding affinity with amino acids in the active site of estrogen receptor β. nih.gov With Gingipain K, this compound revealed a binding free energy of -7.16 kcal/mol and an inhibition constant (Ki) of 5.62 µM. nih.gov

Here is a table summarizing some predicted binding energies of this compound and its derivatives with specific protein targets from computational docking studies:

Analysis of Protein-Ligand Interactions and Amino Acid Networks

Computational studies also delve into the specific interactions between this compound (or its derivatives) and the amino acid residues within the binding site of target proteins. These interactions can include hydrogen bonds, hydrophobic interactions, electrostatic interactions, and van der Waals forces. Analyzing these interactions helps to understand the stability of the protein-ligand complex and identify critical residues for binding.

For example, in the study investigating this compound derivatives as potential antidepressants targeting protein 8FSB, the binding affinity was attributed to interactions with specific amino acids such as SER C:170, GLU C:173, ARG C:169, TRP C:168, and ARG C:65. researchgate.netbiotech-asia.org One derivative, Gati I, was found to interact with the ILE C:268 amino acid residue in the receptor protein. biotech-asia.orgresearchgate.net

Molecular dynamics simulations can further provide insights into the dynamic behavior of the protein-ligand complex over time, assessing the stability of the interactions and conformational changes upon ligand binding. amazonaws.com Studies involving this compound and other compounds with mycobacterial electron transfer flavoprotein oxidoreductase (EtfD) have identified common amino acids involved in interactions, including ARG133, ARG146, ALA155, HIS235, and CYS298. amazonaws.complos.org Hydrogen bonds and hydrophobic interactions are considered critical for stabilizing these protein-ligand complexes. amazonaws.com

Volumetric and Acoustic Investigations of Drug-Surfactant Complexes

Volumetric and acoustic studies, which involve measuring properties like density and sound velocity, are used to investigate the molecular interactions between drugs and surfactants. These measurements allow for the calculation of parameters such as apparent molar volume (ɸV), isentropic compressibility (Ks), and apparent molar isentropic compressibility (ɸK). researchgate.netsci-hub.se Other parameters like partial molar volume (ɸVo), partial molar expansivity (ɸE⁰), specific acoustic impedance (Z), relative association (RA), intermolecular free length (Lf), and sound velocity number (U) can also be obtained. researchgate.netsci-hub.se

Studies on this compound's interactions with ionic surfactants like dodecyltrimethylammonium bromide (DTAB, cationic) and sodium dodecyl sulfate (SDS, anionic) under physiological conditions (phosphate buffer, pH 7.4) have employed these techniques. researchgate.netsci-hub.se The concentration dependence of the calculated parameters is interpreted using models like the cosphere overlap model to understand solute-solute and solute-solvent interactions. researchgate.netsci-hub.se

Voltammetric and Spectroscopic Characterization of Interactions

Electrochemical techniques like cyclic voltammetry and spectroscopic methods such as UV-Visible spectroscopy are employed to further characterize the interactions between this compound and surfactant systems. researchgate.netresearchgate.nettandfonline.comsci-hub.se These methods can provide information on the partitioning and binding of the drug with surfactant micelles. researchgate.nettandfonline.comresearchgate.net

UV-Visible spectroscopy can be used to determine parameters like the critical micelle concentration (CMC) of surfactants in the presence of the drug and to calculate partition coefficients (Kc) and binding constants (Kb) of the drug with ionic micelles. researchgate.nettandfonline.comresearchgate.net Cyclic voltammetry also assists in determining binding parameters and can help predict the location of adsorbed drug molecules within micelles. researchgate.netsci-hub.se

Studies have utilized these techniques to evaluate the interaction of this compound with DTAB and SDS micelles, assisting in predicting where this compound molecules are located within the micelles. researchgate.netsci-hub.se

Interpretation of Solute-Solute and Solute-Solvent Intermolecular Forces

The analysis of volumetric, acoustic, voltammetric, and spectroscopic data allows for the interpretation of the intermolecular forces at play in drug-surfactant systems. This includes understanding the solute-solute, solute-solvent, and solvent-solvent interactions. researchgate.netsci-hub.sescielo.org.co

In this compound-ionic surfactant systems, the interpretation of the concentration dependence of parameters like apparent molar volume and isentropic compressibility using models such as the cosphere overlap model helps to understand the prevailing solute-solute and solute-solvent intermolecular interactions. researchgate.netsci-hub.se For instance, positive values of apparent molar volume have been interpreted as depicting strong forces between surfactant ions and zwitterions of similar compounds, leading to a reduction in electrostriction in the vicinity of these ions. researchgate.net The location of adsorbed this compound molecules within DTAB and SDS micelles, as predicted by voltammetry and UV-Visible spectroscopy, also contributes to understanding these interactions. researchgate.netsci-hub.se Preferential solvation parameters derived from techniques like the inverse Kirkwood-Buff integral can provide a more precise evaluation of molecular interactions and solvent composition around solute molecules. scielo.org.co

Investigation of Hydrogen Bonding and Intermolecular Forces with Nanocarriers (e.g., Silica Nanoparticles)

Investigations into the interaction between this compound and nanocarriers like silica nanoparticles suggest that physical interactions, rather than the formation of new chemical bonds, are primarily responsible for the binding. For instance, when this compound is loaded onto nano-silica, the binding is likely driven by intermolecular forces. frontiersin.orgnih.govresearchgate.net While electrostatic interactions may not be the primary driver, the increase in the solution potential of nano-silica-loaded this compound indicates improved stability. frontiersin.orgnih.gov

Spectroscopic analysis, such as FTIR, has been used to probe the molecular interactions. Red shifts observed in the -OH stretching vibration absorption peak and -CH2 or -CH3 stretching vibration absorption peak suggest that no new bonds are formed between this compound and nano-silica. frontiersin.orgnih.gov However, it is speculated that hydrogen bonding between the silica surface and the N-H group in this compound is a promoted molecular interaction. frontiersin.orgnih.gov

The surface of untreated silica typically possesses polar groups like -OH. nih.gov The negative log P values of this compound indicate a high affinity for a polar environment at a given pH, suggesting that dipole-dipole or dipole-induced dipole electrostatic interactions could also play a role in the interaction between this compound and nano-silica. nih.gov

In the context of other nanomaterials, the self-assembly of small molecules, including signaling molecules, is often driven by non-covalent interactions such as electrostatic, hydrophobic, hydrogen bonding, and van der Waals forces. mdpi.com This highlights the general importance of these intermolecular forces in the interaction between small molecules like this compound and nanomaterial surfaces.

Characterization of Surface Interactions and Film Formation on Nanomaterials

Characterization techniques such as Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), particle size analysis, and Zeta potential measurements have been employed to understand the surface interactions and the potential formation of a drug film on nanocarriers. Based on these characterizations, it has been speculated that this compound can form a film on nano-silica. frontiersin.orgnih.gov

An increase in the average particle size of nano-silica after loading with this compound further supports the idea that this compound is wrapped on the surface of the nano-silica, forming a drug film. frontiersin.orgnih.gov The surface of pure nano-silica solution is negatively charged, which is within the range that provides moderate electrostatic stabilization of suspensions. frontiersin.orgnih.gov Pure this compound solution is also negatively charged. frontiersin.orgnih.gov

Studies involving other types of nanoparticles, such as lipid nanoparticles, also discuss the formation of a film on surfaces, like the corneal surface after topical application, where the lipid core interacts with the tear film's lipid layer. nih.gov This property contributes to the retention of nanocarriers on the ocular surface. nih.gov The morphology of nanoparticles, including their smoothness and spherical shape, is considered important for enhancing the degree of internalization. ijirset.com

Research on the interaction of this compound with iron mineral/water interfaces, specifically goethite and hematite, has revealed different surface complexation patterns. researchgate.net Outer-sphere complexation, primarily involving strong hydrogen-bond interactions between hydroxyl groups on the mineral surface and oxygens of the carboxyl group of this compound, was found to be the main mechanism of adsorption onto goethite. researchgate.net In contrast, inner-sphere complexation, likely forming a bridging bidentate surface complex, dominated the adsorption onto hematite. researchgate.net This indicates that the nature of the nanomaterial surface significantly influences the interaction mechanism.

Mutations within gyrA (DNA Gyrase A Subunit) and Their Impact on Susceptibility

DNA gyrase, a type II topoisomerase, is typically the primary target of fluoroquinolones in Gram-negative bacteria. Mutations in the gyrA gene, encoding the A subunit of DNA gyrase, are a significant mechanism of resistance to this compound. These mutations, often single amino acid substitutions within the QRDR of GyrA, can lead to reduced susceptibility. For instance, studies have shown that single mutations in gyrA can lead to increases in the minimum inhibitory concentration (MIC) of this compound, although sometimes the effect of a single gyrA mutation alone on this compound MIC can be minimal or silent depending on the bacterial species and specific mutation. nih.govpsu.edu However, the presence of a gyrA mutation has been associated with increased MICs of this compound in some strains. vivexia.fr In Clostridium perfringens, mutations in gyrA, particularly changes at Gly-81 to Cys and Asp-87 to Tyr, were selected with this compound. asm.org

Mutations within parC (Topoisomerase IV C Subunit) and Their Contribution to Resistance

Topoisomerase IV, also a type II topoisomerase, is often considered the primary target of fluoroquinolones in Gram-positive bacteria. Mutations in the parC gene, encoding the C subunit of topoisomerase IV (GrlA in Staphylococcus aureus), also contribute to this compound resistance. Single mutations in parC can cause increases in the MIC of this compound. nih.govpsu.edu For example, in S. aureus, single grlBA mutations resulted in two- to fourfold increases in the MIC of this compound. nih.gov In Streptococcus pneumoniae, parC mutations like S79F and S79T have been linked to increased this compound MICs. vivexia.fr Some studies suggest that for this compound, topoisomerase IV is the primary target. nih.govpsu.edu

Cumulative Effects of Dual Mutations on Resistance Levels

High-level resistance to this compound often requires the accumulation of mutations in both gyrA and parC genes. jidc.org The presence of dual mutations in both target enzymes has a synergistic effect, leading to significantly higher levels of resistance compared to single mutations in either gene alone. nih.govpsu.edu For instance, in S. aureus, double mutations in gyrA and grlA or grlB caused a substantial increase in the MIC of this compound. nih.govpsu.edu Studies in Escherichia coli have also shown that isolates with greater levels of resistance often possess double mutations in both gyrA and parC genes. jidc.org The cumulative effect of these mutations underscores the challenge in overcoming resistance once multiple alterations in the target enzymes have occurred.

Here is a table summarizing the impact of single and double mutations on this compound MIC in Staphylococcus aureus:

Characterization of this compound as a Substrate for Efflux Transporters (e.g., P-glycoprotein/P-gp/MDR1/ABCB1, Multidrug Resistance-Associated Protein 2/MRP2/ABCC2/cMOAT)

Research indicates that this compound can be a substrate for certain efflux transporters, including P-glycoprotein (P-gp), also known as MDR1 or ABCB1, and Multidrug Resistance-Associated Protein 2 (MRP2), also known as ABCC2 or cMOAT. nih.govresearchgate.netnih.gov Studies using cell lines overexpressing these transporters have provided evidence for this compound transport. For instance, uptake and transport studies support the hypothesis that this compound is a substrate for both P-gp and MRP2. nih.govresearchgate.netnih.gov Concentration-dependent affinity analysis further suggests this interaction. nih.gov The interaction of this compound with P-gp and MRP2 may represent a possible mechanism for acquired resistance. nih.govresearchgate.netnih.gov Cellular uptake of a model substrate for P-gp, [14C] erythromycin, was shown to increase in the presence of this compound in cells overexpressing P-gp, suggesting this compound interacts with this transporter. nih.govresearchgate.netfrontiersin.org Similarly, studies involving MRP2 have also indicated this compound as a substrate. nih.govresearchgate.netnih.gov

Investigation of Non-Interaction with Specific Efflux Pumps (e.g., Breast Cancer Resistance Protein/BCRP/ABCG2/MXR)

While this compound has been characterized as a substrate for P-gp and MRP2, studies have also investigated its interaction with other efflux pumps, such as Breast Cancer Resistance Protein (BCRP), also known as ABCG2 or MXR. Research suggests that this compound is not a substrate for BCRP. nih.govresearchgate.netnih.gov Uptake studies using cell lines overexpressing BCRP did not show elevated uptake of a BCRP substrate in the presence of increasing concentrations of this compound, indicating a lack of interaction with this specific transporter. nih.govresearchgate.netnih.gov This suggests a degree of selectivity in the efflux pumps that handle this compound.

Role of Efflux Pumps in Acquired Resistance Development

Efflux pumps are a significant contributor to multidrug resistance in bacteria, including resistance to fluoroquinolones like this compound. nih.govoup.comjournalagent.com These transmembrane proteins actively transport antimicrobial agents out of the bacterial cell, thereby reducing the intracellular concentration of the drug to sub-inhibitory levels. nih.govgoogle.com This reduced intracellular concentration can allow bacteria to survive and multiply even in the presence of the antibiotic. nih.gov

Several efflux pumps have been implicated in this compound resistance. Studies have shown that this compound can be a substrate for certain efflux transporters, such as P-glycoprotein (P-gp/MDR1/ABCB1) and multidrug resistance associated protein 2 (MRP2/ABCC2/cMOAT). nih.govresearchgate.netmdpi.com Interaction of this compound with these efflux pumps may represent a mechanism for acquired resistance. nih.govresearchgate.net Overexpression of efflux pumps can lead to a significant reduction in the susceptibility of bacteria to this compound. oup.comjournalagent.com For instance, in Staphylococcus aureus, the NorA efflux pump has been shown to contribute to antibacterial resistance, and increased expression of NorA can lead to a decrease in this compound activity, although this compound appears to be less affected by NorA overexpression compared to some other fluoroquinolones like ciprofloxacin and norfloxacin. oup.com

Research using MDCK cell lines transfected with specific efflux transporters like P-gp, MRP2, and BCRP has provided insights into the interaction of this compound with these pumps. nih.govresearchgate.netnih.gov These studies suggest that this compound is a substrate for P-gp and MRP2 but not for BCRP. nih.govresearchgate.net The possible interactions with P-gp and MRP2 may serve as a mechanism for acquired this compound resistance. nih.govresearchgate.net

In Vitro Synergy of this compound with Efflux Pump Inhibitors

Efflux pump inhibitors (EPIs) are compounds that can block the activity of bacterial efflux pumps, thereby preventing the extrusion of antibiotics and increasing their intracellular concentration. jidc.orgasm.orgmdpi.com Combining antibiotics with EPIs is a promising strategy to overcome efflux-mediated resistance and restore the efficacy of existing antimicrobial agents. journalagent.comjidc.orgasm.orgacs.org

In vitro studies have investigated the synergistic effects of this compound in combination with efflux pump inhibitors against resistant bacterial strains. While this compound itself has been suggested to potentially inhibit efflux pumps nih.govnih.gov, combinations of this compound with known EPIs or other agents have shown synergy. For example, studies have explored the synergy of this compound with other antimicrobial agents, such as cefoperazone and the combination of cefoperazone-sulbactam, against Pseudomonas aeruginosa strains. google.com

Research has also demonstrated the potential for synergy between this compound and ciprofloxacin against ciprofloxacin-resistant Pseudomonas aeruginosa. nih.govnih.gov One proposed mechanism for this synergy is that this compound, being an 8-methoxyfluoroquinolone, might inhibit the efflux pumping of ciprofloxacin by P. aeruginosa. nih.govnih.gov An in vitro study using Etest and time-kill assays showed synergy between ciprofloxacin and this compound against a percentage of tested P. aeruginosa isolates. nih.govnih.govfrontiersin.org

Efflux pump inhibitors like verapamil and chlorpromazine have been shown to reduce the Minimum Inhibitory Concentrations (MICs) of various fluoroquinolones, including this compound, against E. coli and S. aureus strains overexpressing efflux pumps. mdpi.com This highlights the potential of EPIs to potentiate the activity of this compound against resistant bacteria.

Impact of Specific Substituents (e.g., C-8 Methoxy Group) on Antimicrobial Profile and Resistance

Derivatives with Enhanced Binding Affinities to Target Receptors

This compound's primary antibacterial mechanism involves inhibiting bacterial DNA gyrase and topoisomerase IV. nih.govdrugbank.com These enzymes are crucial for maintaining the topological state of bacterial DNA. mdpi.com DNA gyrase is the primary target in many Gram-negative bacteria, while topoisomerase IV is often the preferential target in Gram-positive bacteria like Staphylococcus aureus. mdpi.com

Research has explored the synthesis of this compound derivatives with modified structures to potentially enhance their binding affinities to these bacterial type II topoisomerases. Modifications, particularly at the C-7 piperazine ring, have been investigated with the aim of improving antibacterial activity, including against resistant strains. actascientific.comglobalresearchonline.net

Molecular docking studies have been employed to predict the binding modes and affinities of this compound derivatives to target enzymes like topoisomerase II (DNA gyrase) and topoisomerase IV. globalresearchonline.netresearchgate.net For instance, studies involving N-4 piperazinyl derivatives of this compound have utilized docking simulations with S. aureus topoisomerase-II (DNA gyrase) and E. coli topoisomerase-IV to assess binding affinities. globalresearchonline.net Some synthesized derivatives have shown good binding affinity and interaction with these enzymes, in some cases exceeding that of the parent compound. globalresearchonline.net

Specific structural alterations at the C-7 position have demonstrated improved antibacterial activity, which correlates with enhanced binding to the bacterial topoisomerases. actascientific.comglobalresearchonline.net For example, the addition of a 3,4-dimethylbenzenamine group at the 7th position of the piperazinyl ring in one study resulted in excellent antibacterial activity and improved binding affinity compared to this compound and ciprofloxacin. globalresearchonline.net

While the provided search results highlight the use of docking studies to predict enhanced binding, they primarily focus on the correlation with antibacterial activity. Detailed data tables specifically showcasing enhanced binding affinities (e.g., Ki or IC50 values for enzyme inhibition) of various this compound derivatives to isolated bacterial DNA gyrase or topoisomerase IV were not extensively detailed in the search snippets beyond the context of predicting antibacterial efficacy. However, the principle of modifying the C-7 position to influence interaction with these targets is evident. actascientific.comglobalresearchonline.net

Exploration of this compound Derivatives for Non-Antimicrobial Research Applications (e.g., Antidepressant Potential via Serotonin Reuptake Inhibition)

Beyond their well-established antibacterial properties, fluoroquinolones and their derivatives have been explored for potential non-antimicrobial activities. oup.com This includes investigations into immunomodulatory effects and, more recently, potential neurological applications. nih.govoup.com

One area of emerging research involves exploring this compound derivatives for their potential as antidepressant agents, specifically through the mechanism of serotonin reuptake inhibition. biotech-asia.orgresearchgate.netresearchgate.netdntb.gov.ua Depression is a significant mental health disorder linked to low levels of serotonin in the brain. researchgate.netresearchgate.net Selective serotonin reuptake inhibitors (SSRIs) work by blocking the reuptake of serotonin at the presynaptic membrane, increasing its availability in the synapse to bind to postsynaptic receptors, thereby exerting antidepressant effects. biotech-asia.orgresearchgate.net

In silico molecular docking studies have been conducted to evaluate the potential antidepressant activity of this compound derivatives by assessing their binding affinity to proteins involved in serotonin reuptake, such as the serotonin transporter (SERT), often represented by PDB ID 8FSB in docking studies. biotech-asia.orgresearchgate.netresearchgate.netdntb.gov.ua

A study investigating several this compound derivatives (labeled Gati I to Gati VI) using molecular docking revealed promising binding affinities to the protein 8FSB, a target associated with serotonin reuptake inhibition. biotech-asia.orgresearchgate.netresearchgate.netdntb.gov.ua The results indicated that these derivatives generally exhibited higher binding affinities compared to this compound itself. biotech-asia.orgresearchgate.netresearchgate.netdntb.gov.ua

The binding energies observed in this study were:

These docking scores suggest favorable interactions between the this compound derivatives and the target protein, potentially indicating an inhibitory effect on serotonin reuptake. biotech-asia.orgresearchgate.netresearchgate.netdntb.gov.ua Specifically, derivatives Gati I and Gati II showed the strongest predicted binding affinities. biotech-asia.orgresearchgate.net

These findings from in silico studies suggest that this compound derivatives could serve as potential candidates for antidepressant drug discovery, warranting further in vitro and in vivo investigations to validate these predicted activities. biotech-asia.orgresearchgate.netresearchgate.netdntb.gov.ua This exploration into non-antimicrobial applications highlights the potential for structural modifications of existing drug scaffolds to yield compounds with entirely different therapeutic uses. oup.combiotech-asia.orgresearchgate.net