Metronidazole

Rutas Sintéticas: Metronidazol puede sintetizarse mediante varios métodos, incluida la reducción de 2-metil-5-nitroimidazol con hidrazina o borohidruro de sodio.

Producción Industrial: La producción comercial implica síntesis química, con la reducción del grupo nitro a un grupo amino en condiciones anaeróbicas.

Reduction of Metronidazole

This compound functions as a prodrug, becoming active only upon reduction . The nitro group (-NO2) on the imidazole ring is reduced in anaerobic conditions, which is essential for its antimicrobial activity .

• Reductive Activation: Involves the reduction of the nitro group, leading to imidazole fragmentation and cytotoxicity. This process requires four electrons and occurs in a series of one- or two-electron steps, resulting in transient cytotoxic derivatives . The initial step forms a nitro free radical, followed by nitroso, nitroso free radical, and hydroxylamine derivatives .

• Reductive Inactivation: This pathway involves the reduction of the nitro group to a non-toxic amino derivative. This occurs in two-electron steps, consuming a total of six electrons and is oxygen-insensitive .

The presence of oxygen affects this compound's activity. Oxygen competes for electrons, potentially regenerating this compound in a process called futile cycling .

Oxidation of this compound

This compound undergoes hepatic metabolism, including hydroxylation, oxidation, and glucuronidation, leading to the formation of several metabolites . The two main oxidative metabolites are hydroxy and acetic acid derivatives . The hydroxy metabolite, 1-(2-hydroxy-ethyl)-2-hydroxy methyl-5-nitroimidazole, is considered the major active metabolite .

Radical Reactions

The reduction of the nitro group results in the formation of nitro radicals, which disrupt the DNA of microbial cells, thus inhibiting nucleic acid synthesis . this compound is activated by receiving an electron from reduced ferredoxin, produced by pyruvate synthase in anaerobic organisms, converting it into a highly reactive radical anion .

Degradation Reactions

This compound can be degraded through various methods, including UV photolysis, advanced oxidation processes (AOPs), and electrochemical methods.

• UV and UV/H2O2 Systems: this compound degradation has been systematically compared in UV and UV/H2O2 systems. Hydroxyl radicals (- OH) play a major role in this compound degradation in these systems . The contribution of - OH to this compound degradation was found to be around 90.1% in UV/H2O2 systems .

• Reactions with Hydroxyl and Sulfate Radicals: this compound reacts with hydroxyl (HO- ) and sulfate (SO4- −) radicals, leading to degradation. These reactions can be classified into radical adduct formation (RAF) and hydrogen atom transfer (HAT) . The addition of HO- and SO4- − to the C1 position in the this compound molecule is the most feasible reaction channel .

• Electrochemical Processes: Electrochemical activation of peroxymonosulfate (PMS) can effectively degrade this compound. Singlet oxygen (1O2) may be the dominant reactive radical in electrochemical PMS systems .

Reactions with Acridone

This compound reacts with acridone to form a stable reddish-orange colored complex, which has a maximum absorption at 502 nm . The stoichiometry of the this compound-acridone complex is 1:1. The reaction is spontaneous, as indicated by the negative values of the standard free energy (ΔG°) .

Thermodynamic Parameters for this compound-Acridone Complex

The reaction follows pseudo-first-order kinetics .

Acid-Base Behavior and Speciation

The acid-base behavior and speciation of this compound have been studied to understand its behavior in natural waters .

Table of this compound Reactions

(Note: 1 ≥95% of confidence interval.)

Degradation Pathways

Computational studies, using density functional theory (DFT), have explored the degradation pathways of this compound, revealing the main reaction sites are the -NO2, -CH2OH, and -CH2CH2OH groups . The primary degradation reactions include alcohol group oxidation and addition-elimination reactions on the imidazole ring, which replace the nitro group with hydroxyl radicals .

Photocatalytic Degradation

Photocatalytic processes, such as those using ZnO/AC composites, have been employed to degrade this compound in aqueous solutions . These processes can achieve high removal rates under optimal conditions .

These reactions are critical in understanding this compound's function, metabolism, and environmental impact.

Protozoal Infections

• Trichomoniasis : Metronidazole is the first-line treatment for this sexually transmitted infection.
• Amoebiasis : Effective against Entamoeba histolytica, it is used for intestinal and extraintestinal infections.
• Giardiasis : Treats infections caused by Giardia lamblia.

Anaerobic Bacterial Infections

• Bacteroides species : Commonly involved in intra-abdominal infections.
• Clostridium difficile : Used in treating antibiotic-associated diarrhea caused by this bacterium.

Other Applications

• Rosacea : Topical formulations are used to manage this chronic skin condition.
• Bone and Joint Infections : Effective in treating osteomyelitis and septic arthritis.
• Gynecologic Infections : Used for bacterial vaginosis and other pelvic inflammatory diseases.

Case Study 1: Peripheral Neuropathy

A report documented two cases of peripheral neuropathy linked to prolonged this compound therapy. A 69-year-old woman received a total of 55 grams for diverticular disease, while a 52-year-old male patient received 168 grams for hepatic abscesses. Both patients developed symptoms consistent with peripheral neuropathy after extended use .

Case Study 2: Neurologic Toxicity

In a separate case study, a patient exhibited severe neurologic symptoms such as ataxia and dysarthria following this compound treatment. Magnetic resonance imaging revealed characteristic changes associated with this compound toxicity. The patient's symptoms improved significantly after discontinuation of the drug .

Side Effects

While generally well-tolerated, this compound can cause side effects such as:

• Nausea
• Abdominal pain
• Diarrhea
• Peripheral neuropathy (rare but serious)
• Neurologic events (including seizures)

Data Summary Table

• Metronidazol entra en las bacterias anaeróbicas, donde se activa y se reduce a un radical libre de nitroso de corta duración.
• Este radical interactúa con el ADN, causando pérdida de la estructura helicoidal, rotura de la cadena y muerte bacteriana.

Metronidazole belongs to the nitroimidazole family, which includes analogs like dimetridazole , ronidazole , and synthetic derivatives. Below is a detailed comparison based on pharmacological activity, stability, and clinical utility.

Nitroimidazole Analogs: Dimetridazole and Ronidazole

These compounds share a nitroimidazole core but differ in side-chain modifications, affecting their pharmacokinetics and target specificity.

Analytical Performance in Detection
A UPLC-MS/MS study compared columns for detecting nitroimidazoles in chicken meat:

The C18-HILIC column demonstrated superior accuracy for quantifying residues at 0.5 μg/kg, 50% below the MRL (Maximum Residue Limit) .

5-Nitroimidazole Derivatives

Recent studies synthesized derivatives to enhance efficacy and reduce resistance.

Key Findings :

• Hybrid Derivatives: Coupling this compound with eugenol via triazole connectors improved anti-Trypanosoma cruzi activity, matching benznidazole (a first-line Chagas disease drug) .

Metronidazole is a nitroimidazole antibiotic widely used for its antimicrobial properties against anaerobic bacteria and protozoa. Its biological activity is characterized by its mechanism of action, pharmacokinetics, and associated adverse effects. This article delves into the biological activity of this compound, supported by data tables and case studies.

This compound acts primarily through reductive activation, where it is converted into reactive metabolites that can damage bacterial DNA. This process occurs under anaerobic conditions and involves the following steps:

• Reduction of Nitro Group : this compound is reduced to form nitro free radicals, which can interact with DNA, leading to strand breaks and ultimately cell death.
• Cytotoxicity : The activated metabolites inhibit DNA synthesis and repair mechanisms in susceptible organisms, contributing to its bactericidal effects .

Antimicrobial Activity

This compound exhibits a broad spectrum of activity against anaerobic bacteria, including Bacteroides, Clostridium, and Fusobacterium. Research indicates that its antimicrobial effect is bactericidal and independent of the growth rate of the bacteria .

Table 2: Antimicrobial Spectrum of this compound

Pharmacokinetics

This compound is well absorbed orally, with peak plasma concentrations occurring within 1-2 hours post-administration. It has a volume of distribution that allows it to penetrate well into tissues, including the central nervous system (CNS). The drug undergoes hepatic metabolism, primarily through oxidation, followed by renal excretion .

Adverse Effects and Neurotoxicity

While this compound is effective, it is associated with several adverse effects, particularly neurotoxicity. A nested case-control study found an increased risk of neurologic events in patients treated with this compound compared to those treated with clindamycin. The odds ratio was reported as 1.72 for any neurologic event .

Case Study: this compound-Induced Encephalopathy

A notable case involved a 68-year-old female who developed confusion after one week on this compound. MRI results were negative for lesions typically associated with encephalopathy. Upon discontinuation of the drug, her symptoms improved significantly within days .

Resistance Mechanisms

Resistance to this compound has been documented in various bacterial strains, particularly among Helicobacter pylori and Bacteroides fragilis. Mechanisms include:

• Reductive Inactivation : Some bacteria can reduce this compound to non-toxic forms.
• Efflux Pumps : Enhanced efflux mechanisms can expel this compound from bacterial cells before it exerts its effects .