Sulfadiazine

Competitive Inhibition of p-Aminobenzoic Acid (PABA) in Folic Acid Synthesis Pathway

This compound functions as a competitive inhibitor of the bacterial enzyme dihydropteroate synthetase (DHPS). drugbank.comtoku-e.compatsnap.compatsnap.comncats.iodrugbank.compatsnap.comwisdomlib.orgnih.gov This inhibition occurs because this compound structurally resembles p-aminobenzoic acid (PABA), a natural substrate for DHPS. patsnap.compatsnap.comncats.iodrugbank.compatsnap.comwisdomlib.orgnih.gov By mimicking PABA, this compound competes for the active site of the DHPS enzyme, thereby preventing the enzyme from incorporating PABA into dihydropteroate. patsnap.compatsnap.comncats.iodrugbank.compatsnap.comwisdomlib.org This blocked reaction is a necessary step in the synthesis of folic acid within these microorganisms. drugbank.comtoku-e.comncats.iodrugbank.compatsnap.com

Essentiality of Folic Acid Synthesis for Bacterial Growth and Metabolism

Folic acid, specifically its active form tetrahydrofolate (THF), is an indispensable cofactor for enzymes involved in one-carbon metabolism within bacteria. nih.govfiveable.menih.govasm.orgresearchgate.netnih.gov This metabolic pathway is vital for the synthesis of critical cellular components, including nucleotides (the fundamental building blocks of DNA and RNA), purines, pyrimidines, and certain amino acids such as methionine, serine, and glycine. patsnap.compatsnap.compatsnap.comnih.govfiveable.measm.orgresearchgate.netnih.gov Furthermore, N-formylmethionine, derived from folate, is essential for the initiation of bacterial protein translation. asm.org

Unlike humans, who acquire folic acid from dietary sources, most bacteria must synthesize it de novo. patsnap.compatsnap.compatsnap.comnih.gov This fundamental difference renders the bacterial folic acid synthesis pathway an excellent and selective target for antibacterial agents like this compound. patsnap.com The disruption of folic acid production by this compound consequently impairs bacterial DNA, RNA, and protein synthesis, leading to the inhibition of their growth and proliferation. patsnap.compatsnap.compatsnap.com It is important to note that this compound is primarily bacteriostatic, meaning it inhibits the growth and multiplication of bacteria rather than directly killing them, thus relying on the host's immune system to eliminate the inhibited pathogens. patsnap.compatsnap.comwikipedia.org

Activity Against Gram-Positive Bacteria (e.g., Staphylococcus aureus, Streptococcus pneumoniae)

This compound is effective against a majority of Gram-positive cocci. wisdomlib.org This includes notable pathogens such as Staphylococcus aureus and Streptococcus pneumoniae. taylorandfrancis.compfizer.compfizermedicalinformation.comwoundsinternational.comasm.org In in vitro testing, silver this compound has shown high sensitivity against Staphylococcus aureus, with 100 out of 101 tested strains being sensitive at concentrations of 50 µg/mL and 100 µg/mL. pfizer.compfizermedicalinformation.com Similarly, β-Hemolytic Streptococcus strains (4 out of 4 tested) demonstrated sensitivity to silver this compound at these concentrations. pfizermedicalinformation.com

Activity Against Gram-Negative Bacteria (e.g., Escherichia coli, Pseudomonas aeruginosa, Enterobacter, Klebsiella)

This compound demonstrates efficacy against numerous Gram-negative bacteria. drugbank.comncats.iowisdomlib.org This includes common pathogens such as Escherichia coli, Pseudomonas aeruginosa, Enterobacter species, and Klebsiella species. drugbank.comwisdomlib.orgtaylorandfrancis.compfizer.compfizermedicalinformation.comasm.orgnih.gov In vitro studies with silver this compound have shown high rates of sensitivity among these bacteria. For instance, 130 out of 130 Pseudomonas aeruginosa strains, 63 out of 63 Escherichia coli strains, 48 out of 50 Enterobacter species strains, and 53 out of 54 Klebsiella species strains were sensitive to silver this compound at a concentration of 50 µg/mL. pfizer.compfizermedicalinformation.com

Efficacy against Yeast (Candida albicans)

Silver this compound has shown moderate activity against yeast, including Candida albicans. drugbank.comtaylorandfrancis.compfizer.commdpi.compfizermedicalinformation.com Research indicates that sulfonamide drugs, including this compound, can exhibit synergistic activity when combined with azole antifungals against azole-resistant Candida albicans strains. contagionlive.com While silver this compound has demonstrated effectiveness in reducing bacterial bioburden in polymicrobial infections involving Pseudomonas aeruginosa and Candida albicans, its efficacy in reducing C. albicans proliferation may be less pronounced, suggesting that additional antifungal treatments might be necessary for complete eradication of Candida infections. researchgate.netwounds-uk.comoup.com

Activity against Parasitic Organisms (Toxoplasma gondii, Plasmodium falciparum)

This compound demonstrates significant activity against various parasitic organisms, notably Toxoplasma gondii and Plasmodium falciparum.

In the context of Toxoplasmosis , this compound is a cornerstone therapy, frequently administered in combination with pyrimethamine. Its antiparasitic action stems from the inhibition of dihydropteroate synthase (DHPS), an enzyme critical for the de novo folate biosynthesis pathway in T. gondii. This interruption of folate synthesis subsequently blocks the production of nucleic acids, which are vital for parasite survival and replication asm.orgmdpi.compatsnap.commedscape.com. Studies have indicated that this compound treatment can mitigate metabolic disturbances induced by T. gondii infection and may promote the differentiation of tachyzoites into bradyzoite-containing cysts asm.org. While effective, the development of resistance in T. gondii has been linked to mutations within the DHPS gene mdpi.comnih.gov.

Against Plasmodium falciparum , the causative agent of malaria, this compound functions as an antifolate by competitively inhibiting the parasite's dihydropteroate synthase (DHPS), thereby obstructing DNA synthesis nih.govbiorxiv.org. This mechanism is characteristic of sulfa drugs, which interfere with the folate metabolism cycle by acting as competitive inhibitors of p-aminobenzoic acid (PABA) nih.govdrugbank.com. This compound exhibits selective toxicity, effectively killing actively replicating asexual blood stages of Plasmodium parasites while sparing non-replicating gametocytes. This differential effect has led to its use as a tool for enriching gametocyte samples in rodent malaria models nih.govbiorxiv.orgnih.gov. However, this compound treatment has been shown to significantly impact host-to-vector transmission of the parasite nih.govbiorxiv.orgnih.gov. Investigations into metal complexes of this compound, such as the Fe(III) complex, suggest they may exhibit enhanced activity against resistant strains of P. falciparum compared to this compound alone ajol.info.

This compound's Impact on Inflammatory Mediators and Enzymes (e.g., TNFα, IL1b, COX-1, COX-2, 5-LOX)

This compound demonstrates an anti-inflammatory effect by modulating the levels of key inflammatory mediators and enzymes. Research indicates its capacity to suppress the inflammatory response at a molecular level by influencing the expression of inflammation-related genes, including Tumor Necrosis Factor alpha (TNFα), Interleukin 1 beta (IL-1β), Cyclooxygenase-1 (COX-1), Cyclooxygenase-2 (COX-2), and 5-Lipoxygenase (5-LOX) mdpi.comnih.govdntb.gov.uaresearchgate.netnih.gov. Specifically, this compound has been shown to exhibit inhibitory activity against COX-1, COX-2, and 5-LOX enzymes nih.govnih.gov.

Molecular Modeling and Simulation Studies of Binding Interactions

Molecular modeling and simulation studies have provided valuable insights into the binding interactions of this compound with various targets, including COX-1, COX-2, and 5-LOX. Computational analyses, such as molecular docking and dynamics simulations, have revealed the key binding interactions that explain the activity profiles of this compound mdpi.comnih.govdntb.gov.uanih.govresearchgate.net. This compound exhibits a docking pattern within the COX-2 active site that is comparable to that of the reference drug celecoxib mdpi.com. Similarly, in the COX-1 active site, its docking pose resembles that of celecoxib and the crystallized inhibitor mofezolac mdpi.com. The 2-sulfamoylamino pyrimidine group of this compound has been identified as a crucial binding moiety, participating in interactions across all three investigated targets: COX-1, COX-2, and 5-LOX mdpi.com. Molecular dynamics simulations further support the robust stability of these interaction profiles mdpi.comresearchgate.netresearchgate.netfrontiersin.org.

Differential Inhibitory Activity against COX/LOX Pathway

This compound exhibits a distinct and balanced inhibitory activity profile against the Cyclooxygenase (COX) and Lipoxygenase (LOX) pathways. Experimentally, this compound has demonstrated a COX-2/COX-1 selectivity ratio of 3.6, which is higher than that observed for celecoxib (2.9) mdpi.com. While this compound shows weaker inhibitory activity against COX-2 (IC50 = 5.27 μM) compared to the selective COX-2 inhibitor celecoxib (IC50 = 1.94 μM), it presents a more balanced inhibitory effect across the COX/LOX pathway nih.govresearchgate.netnih.gov. Notably, this compound exhibits a greater affinity towards 5-LOX (IC50 = 19.1 μM) compared to COX-1 (IC50 = 18.4 μM) nih.govresearchgate.netnih.gov. This indicates that its activity profile favors 5-LOX inhibition at the expense of COX-1 inhibition, suggesting a balanced inhibitory action against the 5-LOX/COX-1 enzymes mdpi.comnih.govdntb.gov.uanih.gov.

Table 1: Experimental IC50 Values and Selectivity Ratios for this compound and Celecoxib against COX-1, COX-2, and 5-LOX mdpi.comnih.govnih.gov

Note: IC50 values represent the half-maximal inhibitory concentration. Selectivity ratios are calculated as IC50(COX-1)/IC50(COX-2) and IC50(COX-1)/IC50(5-LOX) respectively.

Heterocyclic Compounds Bearing this compound Moiety

The incorporation of heterocyclic rings into the this compound structure has yielded promising results in developing new compounds with improved biological activities. Researchers have synthesized new series of ether and thioether derivatives of this compound by reacting this compound with chloroacetyl chloride, followed by treatment with various phenols and thiols. These synthesized derivatives have demonstrated superior antibacterial activity against both Gram-positive and Gram-negative bacteria, including strains like Candida albicans, when compared to established antibiotics such as amoxicillin and ciprofloxacin. uobaghdad.edu.iq

Another approach involves the synthesis of N-substituted this compound derivatives featuring different heterocyclic rings, such as 4-oxo-1,4-dihydroquinazolin and 4-oxo-2H-benzo uobaghdad.edu.iqCurrent time information in Bangalore, IN.thiazin. These compounds have been synthesized via condensation reactions and characterized using spectroscopic techniques like FT-IR, 1H-NMR, and 13C-NMR. Notably, some of these derivatives have exhibited anti-mycobacterial activity against Mycobacterium tuberculosis H37Rv, with minimum inhibitory concentrations (MICs) ranging from 4-16 µg/mL for the most active compounds.

Further research has explored the preparation of new heterocyclic derivatives by treating this compound with aromatic aldehydes to form imine derivatives, which then undergo cycloaddition reactions to produce azetidin-2-one derivatives. ekb.egekb.eg Other synthetic routes include the formation of pyridazine, pyrazolines, and pyrimidine compounds by reacting this compound derivatives with various reagents under ultrasound irradiation. edu.krd These heterocyclic compounds have shown promising antimicrobial activities against human pathogenic bacteria strains like Escherichia coli and Staphylococcus aureus, as well as fungi such as Candida albicans. edu.krd

Schiff Base Derivatives of this compound

Schiff bases, formed by the condensation of an amine with an aldehyde or ketone, represent another significant class of this compound derivatives. A series of (E)-4-(benzylideneamino)-N-(pyrimidin-2-yl)benzenesulfonamide compounds have been synthesized from this compound and substituted aromatic aldehydes. nih.govresearchgate.net These derivatives have been investigated for their urease inhibitory activity, with some compounds demonstrating potent inhibition. For instance, one active compound exhibited an IC₅₀ value of 2.21 ± 0.45 µM against urease, showing significantly higher potency than the standard thiourea (20.03 ± 2.06 µM). nih.gov

Additionally, this compound-salicylaldehyde-based Schiff bases have been synthesized and evaluated for their antimicrobial activity against a broad panel of pathogens, including Gram-positive and Gram-negative bacteria, yeasts, moulds, and mycobacteria. mdpi.com The genus Staphylococcus, including methicillin-resistant S. aureus (MRSA), showed high susceptibility to these derivatives, with MIC values as low as 7.81 µM. mdpi.com

Sulfonamide-Linked Drug Derivatives (e.g., with Ciprofloxacin, Amantadine)

The concept of linking this compound to other established drugs via sulfonamide linkages has been explored to create novel hybrid compounds with potentially enhanced or broader therapeutic profiles. New series of sulfonamide-based drugs have been synthesized by reacting this compound with suitably substituted sulfonyl chlorides to construct sulfonamide linkages. mdpi.com This approach has been applied to versatile drugs such as ciprofloxacin and amantadine, forming sulfonamide-linked derivatives. mdpi.com For this compound, where the amine function is less reactive, reflux conditions in pyridine were necessary for the reaction to proceed smoothly, yielding excellent results. mdpi.com These sulfonamide-linked derivatives have been investigated for their inhibitory activity against enzymes like Jack Bean Urease. mdpi.com

Combination with Pyrimethamine for Toxoplasmosis Treatment

The combination of this compound and pyrimethamine is considered the gold standard for treating toxoplasmosis, an infection caused by the protozoan parasite Toxoplasma gondii. mdpi.comconsensus.appasm.org This regimen targets the active tachyzoite stage of the infection by inhibiting the folate pathway, which is crucial for DNA synthesis in the parasite. asm.orgnih.gov

Studies in rhesus monkeys with congenital Toxoplasma gondii infection demonstrated the efficacy of this combination. Treatment with pyrimethamine (1 mg/kg/day) and this compound (50 mg/kg/day) orally, supplemented with folinic acid, led to the parasite no longer being detectable in amniotic fluid samples 10 to 13 days after treatment initiation. asm.org Furthermore, T. gondii was not found in neonates at birth in treated groups, unlike in untreated controls. asm.org Both drugs were found to cross the placenta effectively, with concentrations in fetal serum for pyrimethamine ranging from 0.05 to 0.14 µg/ml and for this compound from 1.0 to 5.4 µg/ml. asm.org Pyrimethamine also showed accumulation in brain tissue, with concentrations three to four times higher than in serum, while this compound reached about 30% of its serum concentration in brain tissue. asm.org

In a model of long-term chronic T. gondii infection in C57BL/6 mice, combined this compound-plus-pyrimethamine (S+P) therapy significantly reduced brain cyst load, neuroinflammation, and blood-brain barrier disruption. nih.gov This reduction in parasitic burden and associated inflammatory responses corresponded with the resolution of locomotor alterations, anxiety, and depressive-like behaviors, and partial amelioration of hyperactivity and habituation memory loss. nih.gov

Alterations in Dihydropteroate Synthetase

Sulfonamides exert their antibacterial effect by competitively inhibiting dihydropteroate synthetase (DHPS), an enzyme encoded by the folP gene biorxiv.orgrupahealth.compatsnap.comfrontiersin.orgnih.govdrugbank.com. DHPS is critical for the condensation of para-aminobenzoic acid (pABA) and 6-hydroxymethyl-7,8-dihydropterin pyrophosphate (DHPP) to produce 7,8-dihydropteroate, a precursor in the folate synthesis pathway biorxiv.orgnih.gov. This compound structurally mimics pABA, thereby binding to the DHPS active site and blocking its natural substrate patsnap.comdrugbank.compatsnap.com.

Resistance through this mechanism typically involves spontaneous mutations within the chromosomal folP gene, leading to amino acid substitutions in the DHPS enzyme biorxiv.orgrupahealth.comfrontiersin.orgnih.govpnas.orgmcmaster.ca. These mutations alter the enzyme's active site, reducing its affinity for sulfonamides while largely preserving its ability to bind to its natural substrate, pABA rupahealth.comfrontiersin.org. This discrimination capacity is achieved by increasing the Michaelis constant (K_M) for sulfonamides biorxiv.orgrupahealth.com. For instance, studies on Staphylococcus aureus DHPS have identified specific mutations like F17L, S18L, T51M, E208K, and KE257_dup that contribute to sulfonamide resistance frontiersin.org. Similarly, in Plasmodium falciparum, amino acid differences in DHPS have been linked to varying levels of sulfadoxine (another sulfonamide) resistance, with K_i values differing by almost three orders of magnitude between sensitive and highly resistant isolates pnas.org. Some resistance-conferring alterations involve insertions, such as a Phe-Gly sequence in certain Sul enzymes, which modifies the pABA-interaction region, leading to a significant (over 1000-fold) loss in sulfonamide binding affinity without compromising the rate of dihydropteroate biosynthesis biorxiv.org.

Horizontal Gene Transfer (HGT) and Mobile Genetic Elements (MGEs)

Horizontal gene transfer (HGT) is a predominant mechanism for the rapid dissemination of sulfonamide resistance among bacterial populations biorxiv.orgrupahealth.comfrontiersin.orgnih.govfrontiersin.orgasm.orgmdpi.comnih.gov. This process involves the transfer of genetic material, including antibiotic resistance genes (ARGs), between unrelated bacteria rupahealth.commdpi.com.

The most well-characterized ARGs conferring sulfonamide resistance are the sul genes (sul1, sul2, sul3, and sul4) rupahealth.comnih.govnih.govfrontiersin.orgd-nb.infoplos.org. These genes encode alternative dihydropteroate synthase enzymes (referred to as Sul enzymes) that are intrinsically insensitive to sulfonamides biorxiv.orgrupahealth.com. The Sul enzymes possess a modified active site that allows them to function efficiently in folate synthesis while being largely unaffected by the presence of sulfonamides biorxiv.orgnih.gov.

A critical factor facilitating HGT is the association of sul genes with mobile genetic elements (MGEs), such as plasmids, transposons, and integrons biorxiv.orgrupahealth.comfrontiersin.orgnih.govfrontiersin.orgasm.orgmdpi.comfrontiersin.orgd-nb.infoplos.orgnih.govmdpi.com. Plasmids, which are extrachromosomal DNA molecules, can be readily transferred between bacterial cells through conjugation, a direct cell-to-cell contact mechanism frontiersin.orgfrontiersin.orgmdpi.comnih.gov. Transposons are DNA sequences that can move to different locations within a genome, and integrons are genetic elements capable of capturing and expressing gene cassettes, often including ARGs asm.orgmdpi.com.

Class 1 integrons, in particular, are frequently found co-locating with sul1 and sul2 genes, significantly contributing to their widespread dissemination in both clinical and environmental settings nih.govasm.orgmdpi.comfrontiersin.orgd-nb.infonih.govasm.org. While sul1, sul2, and sul3 are commonly associated with MGEs, recent research has identified sul4, a newer mobile sulfonamide resistance gene, which in some marine bacterial isolates, was not accompanied by known MGEs, suggesting clonal transfer in those specific cases nih.govfrontiersin.orgd-nb.infodoaj.org. However, sul4 has also been reported in integrons, indicating its potential for broader mobility d-nb.info.

Vertical Gene Transfer

Vertical gene transfer (VGT) refers to the inheritance of genetic material, including resistance genes, from parent bacterial cells to their progeny during cell division rupahealth.comfrontiersin.orgmdpi.com. This mechanism plays a fundamental role in the maintenance and accumulation of resistance within a bacterial lineage once it has acquired resistance determinants, whether through spontaneous mutation or HGT rupahealth.commdpi.com.

Spontaneous mutations in the chromosomal folP gene, which lead to altered DHPS enzymes, are classic examples of resistance arising via VGT rupahealth.commdpi.com. While HGT is a rapid and efficient way for bacteria to acquire novel resistance traits from diverse sources, VGT ensures the perpetuation of these advantageous traits within a population, especially under continued selective pressure from antibiotics. Studies have indicated that while HGT is the primary driver for the dissemination of sul genes, VGT contributes to their stability and persistence within bacterial populations frontiersin.org.

Emergence in Clinical Settings (e.g., Burns Units)

The extensive use of sulfonamides has directly contributed to the significant development of bacterial resistance across various clinical settings rupahealth.com. Burns units, in particular, have historically served as hotspots for the emergence and dissemination of this compound resistance due to the routine application of topical antimicrobial agents like silver this compound for infection prophylaxis and treatment wounds-uk.comnih.govinstitutobeatrizyamada.com.br.

Early observations in burns units noted a substantial increase in the proportion of this compound-resistant Gram-negative bacilli following the introduction of silver this compound cream wounds-uk.comnih.gov. When sulfonamide treatment was discontinued in these wards, the incidence of resistant strains, particularly Klebsiella species, decreased nih.gov. Studies have shown that Staphylococcus aureus and coliforms were frequently isolated from wounds treated with silver this compound, with a high percentage of these isolates exhibiting sulfonamide resistance wounds-uk.com. Furthermore, transferable resistance to this compound has been demonstrated in various species, including Klebsiella sp. and Escherichia coli, isolated from burn patients, highlighting the role of HGT in clinical settings nih.gov.

Table 1: Prevalence of Multidrug-Resistant Organisms in Burn Units (2011-2019) frontiersin.org

Prevalence and Dissemination in Environmental Reservoirs (e.g., Soil, Water, Manure)

Environmental reservoirs play a crucial role in the persistence and dissemination of sulfonamide resistance. Antibiotic resistance genes (ARGs) associated with sulfonamides are widely detected in various environmental matrices, including agricultural soils, water bodies, and animal manure rupahealth.comnih.govfrontiersin.orgplos.orgnih.govmdpi.comasm.orgasm.orgoup.com.

The application of animal manure as fertilizer is a significant contributor to the spread and abundance of ARGs in agricultural soils plos.orgoup.com. Manure from animals treated with sulfonamides, such as this compound, can introduce resistant bacteria and their genes into the environment asm.orgoup.com. Studies in the United Kingdom revealed that phenotypic resistance to sulfachloropyridazine (SCP) was significantly higher in bacterial isolates from pig slurry and post-application soil compared to pre-application soil asm.org.

The sul1, sul2, and sul3 genes are commonly found in manured agricultural soils and pig slurry plos.orgasm.orgasm.org. The prevalence of these sul genes can vary depending on the specific environment and the type of animal manure applied. For instance, in soils from Jiangsu Province, China, the frequency of sul genes in pig-manured soil DNA was sul1 > sul2 > sul3, while in chicken-manured soil DNA, it was sul2 > sul1 > sul3 plos.org.

Table 2: Prevalence of sul Genes in Manured Soil Isolates plos.orgasm.org

Sulfonamide-resistant pathogens identified in environmental reservoirs include Shigella flexneri, Aerococcus spp., Acinetobacter baumannii, Psychrobacter, Enterococcus, Bacillus spp., and Pseudomonas plos.orgasm.orgasm.org. This highlights the potential for environmental reservoirs to act as sources for human exposure to resistant bacteria.

Wastewater discharge also contributes significantly to the dissemination of sulfonamide resistance. Pharmaceutical wastewaters and municipal wastewater treatment plants (WWTPs) have been shown to contain varying amounts of antibiotics, including this compound, and high prevalences of sul1 and sul2 genes nih.govmdpi.com. Even at low concentrations, antibiotics in wastewater can exert selective pressure, promoting the evolution and spread of ARGs among environmental bacteria and potentially to human pathogens mdpi.com.

Concentrations in Surface and Ground Waters, Wastewater, and Sewage Sludge

This compound and other sulfonamides have been detected in various water compartments and environmental matrices at varying concentrations. In wastewater from treatment plants or animal farms, sulfonamide concentrations typically range from 2 to 60 µg/L wikipedia.org. More specifically for this compound, concentrations of approximately 0.019 µg/L have been detected in processed sewage in Canadian cities, while effluents after secondary treatment in Germany showed detection levels of 0.081 µg/L guidetopharmacology.org.

Surface waters have reported sulfonamide concentrations ranging from 10 ng/L to 1.4 µg/L wikipedia.org. This compound specifically has been found at a maximum concentration of 0.056 µg/L in the surface water of Poyang Lake, China, and at 502.43 ng/L in other surface water samples guidetopharmacology.orgguidetopharmacology.org. In groundwater, sulfonamide concentrations are generally below 10 ng/L wikipedia.org.

In soil matrices, particularly those adjacent to livestock farms, residual this compound concentrations can reach up to 2.45 mg/kg, with other fields showing ranges of 100–1000 µg/kg wikipedia.org. This compound has also been detected in sewage sludge uni.lu.

Table 1: Reported Concentrations of this compound in Environmental Matrices

Phototransformation Processes and Half-Life in Surface Water

Photolysis is a crucial degradation pathway for this compound in surface waters wikipedia.orgwikipedia.orgwikipedia.org. Studies indicate that direct photolysis is the primary mechanism for this compound photodegradation in ultrapure water wikipedia.org. Several environmental factors can significantly influence the efficiency of this compound phototransformation. Higher pH values, as well as the presence of humic substances, sodium chloride (NaCl), or synthetic sea salts, have been shown to enhance its degradation wikipedia.org.

Under typical surface water conditions, comparable to those found in the Swiss river Thur, the estimated phototransformation half-life for this compound ranges from 3 to 13 days nih.govwikipedia.orgwikipedia.org. In controlled laboratory settings, the half-life in ultrapure water was determined to be 6.76 hours at pH 7.3 and 12.2 hours at pH 6.3 wikipedia.org. Photodegradation was found to be notably faster in environmental matrices such as sewage treatment plant effluent, fresh water, and brackish water, with half-lives ranging between 2.3 and 3.48 hours, compared to ultrapure water wikipedia.org. Mathematical simulations predict that this compound's half-life in natural aqueous systems can vary from less than 2 to approximately 90 days, influenced by water depth and the concentration of key species like dissolved organic carbon (DOC), bicarbonate (HCO3-), and nitrite (NO2-) fishersci.camims.com.

Table 2: Phototransformation Half-Lives of this compound

Biodegradation in Environmental Matrices

This compound is generally considered not readily biodegradable wikipedia.orgmims.com. In biodegradation experiments, the decrease in this compound concentrations was observed to be minimal, around 4% wikipedia.org. Hydrolytic experiments conducted at typical environmental pH values also indicate its resistance to degradation through hydrolysis wikipedia.org.

Despite its general recalcitrance, specific microbial degradation has been observed under certain conditions. For instance, the bacterium Enterobacter cloacae T2, when immobilized on bagasse, demonstrated a significant degradation potential, achieving 78.19% degradation of this compound in soil under optimal conditions (28 °C and pH 3.5) wikipedia.orgwikipedia.org. Another study reported that Microbacterium lacus strain SDZm4 was capable of completely degrading this compound within 10 days in soil that had been treated with manure containing the antibiotic wikipedia.org.

Effects on Crustaceans (Daphnia magna) and Fish (e.g., Zebrafish)

Effects on Crustaceans (Daphnia magna) this compound exhibits both acute and chronic toxicity to the crustacean Daphnia magna. The LC50 (lethal concentration for 50% of the population) for Daphnia magna exposed to this compound was determined to be 1.884 mg/L fishersci.be. The toxicity of this compound to Daphnia magna is significantly influenced by pH, with higher toxicity observed at lower pH values. The 48-hour EC50 (effective concentration for 50% of the population) values were reported as 27.2 mg/L at pH 6.0, 188 mg/L at pH 7.5, and 310 mg/L at pH 8.5 nih.govnih.govnih.gov. This increased toxicity at lower pH is attributed to a higher fraction of the un-ionized form of this compound, which can more readily permeate cell membranes nih.govnih.gov. For chronic toxicity, the No Observed Effect Concentration (NOEC) for Daphnia magna is 6 mg/L mims.comwikidata.org. Furthermore, the bioconcentration factor (on a dry weight basis) for this compound in Daphnia magna was found to be 50 at pH 6.0 and 36 at pH 8.5 nih.govnih.gov.

Table 3: Toxicity of this compound to Daphnia magna

Effects on Fish (e.g., Zebrafish) Exposure of fish, such as zebrafish (Danio rerio), to sulfonamides, including this compound, has been linked to various adverse effects. These include an increased heart rate and abnormal swimming behavior fishersci.be. This compound has also been identified as a typical inducer of metabolic enzymes in fish, suggesting a potential ecotoxicological risk fishersci.be. Even at low concentrations, sulfonamides like sulfadimidine (a synonym for sulfamethazine) at 0.001 mg/L have been shown to cause significant toxic effects on the spontaneous movements, heartbeats, and hatching of zebrafish embryos fishersci.cawikidata.org. Furthermore, exposure can lead to characteristic malformations in embryos and larvae, such as pericardial edema, yolk sac edema, hemoglutinations, tail deformation, and swim bladder defects fishersci.cawikidata.org. The No Observed Effect Concentration (NOEC) for chronic toxicity in zebrafish is 0.157 mg/L mims.comwikidata.org.

Table 4: Toxicity of this compound to Zebrafish