Metronidazole: Chemical Structure, Mechanism of Action, SAR, Synthesis, Uses & Side

Chemical formula:

• C6H9N3O3

Structure of Metronidazole

Mechanism of action:

• Metronidazole is a nitroimidazole antibiotic and antiprotozoal agent. It is selectively taken up by anaerobic microorganisms and protozoa, where it undergoes a reduction reaction, forming toxic intermediates that damage the DNA structure and inhibit nucleic acid synthesis, leading to cell death.

Structure-Activity Relationship (SAR) of Metronidazole:

1.Nitroimidazole Core:

• The core of Metronidazole's structure is a nitroimidazole ring. The nitro group at the 5-position of the imidazole ring is crucial for its antimicrobial activity. This group is reduced in anaerobic conditions, which is key to the drug's mechanism of action.

2.Side Chain at 1-Position of Imidazole:

• The side chain attached to the 1-position of the imidazole ring plays a significant role in its pharmacological activity. In Metronidazole, this is an ethyl group.

3.Polar Nature:

• The polar nature of Metronidazole, primarily due to the nitro group, aids in its solubility and absorption.

4.Modifications:

• Modifications to the nitroimidazole core can alter the drug's spectrum of activity and pharmacokinetics. However, the nitro group and the imidazole ring structure are essential for the antimicrobial activity.

Mentronidazole Overview

Synthesis of Metronidazole:

• The synthesis of Metronidazole typically involves the following chemical reactions:

1.Formation of Imidazole Ring:

• The synthesis begins with the formation of an imidazole ring, which can be achieved through a series of steps starting from simple precursors like 1,2-diaminoethane and glyoxal.

2.Introduction of Nitro Group:

• Once the imidazole ring is formed, a nitro group is introduced at the 5-position. This is often done using a nitrating agent like nitric acid:

• Imidazole + HNO3 → 5-Nitroimidazole

3.Attachment of Ethyl Side Chain:

• Finally, the ethyl side chain is attached at the 1-position of the imidazole ring. This step might involve a simple alkylation reaction:

• 5-Nitroimidazole + Ethylating Agent → Metronidazole

• The specific conditions and reagents used in these reactions can vary, but these steps provide a general overview of how Metronidazole is synthesized.

Uses:

• Metronidazole is used to treat various infections caused by anaerobic bacteria and protozoa, including bacterial vaginosis, trichomoniasis, giardiasis, and amoebic dysentery.

Side effects:

• Common side effects include gastrointestinal disturbances (nausea, vomiting, diarrhea), metallic taste, headache, and dizziness. In rare cases, it may cause peripheral neuropathy or seizures.