Chemical formula:
C16H13N3O3
Mechanism of action:
Mebendazole, another benzimidazole, works by inhibiting the polymerization of tubulin in the parasite, disrupting microtubule formation and interfering with glucose uptake, ultimately leading to the death of the worm.
Structure-Activity Relationship (SAR) of Mebendazole:
1.Benzimidazole Core:
The core structure of Mebendazole is a benzimidazole ring. This moiety is crucial for its anthelmintic activity, as it binds to the parasitic worm's beta-tubulin, inhibiting its microtubule formation, which is essential for glucose uptake and digestive processes.
2.Carbamate Group:
The carbamate group at the 5-position of the benzimidazole ring is significant for the drug's efficacy. This group enhances the binding affinity to the parasite's tubulin.
3.Substituents on the Benzimidazole Ring:
The substituents on the benzimidazole ring, particularly the methoxy group at the 2-position and the carbamoyl group at the 5-position, are important for the drug's activity and specificity.
4.Lipophilicity:
The lipophilic nature of Mebendazole, attributed to its aromatic and aliphatic groups, aids in its absorption and distribution in the host's body, allowing it to reach the parasites effectively.
Synthesis of Mebendazole:
The synthesis of Mebendazole involves a series of chemical reactions, which can be broadly outlined as follows:
1.Formation of Benzimidazole Core:
The synthesis usually starts with the formation of a benzimidazole core. This can be achieved by reacting o-phenylenediamine with a carboxylic acid derivative (like formic acid or acetic acid) under certain conditions:
o-Phenylenediamine+Carboxylic Acid Derivative→Benzimidazole
2.Introduction of Carbamate Group:
The next step involves the introduction of the carbamate group. This is typically done by reacting the benzimidazole core with an appropriate isocyanate compound:
Benzimidazole+Isocyanate → Carbamate-Substituted Benzimidazole
3.Substitution with Methoxy Group:
Finally, a methoxy group is introduced at the 2-position of the benzimidazole ring. This step might involve a methylation reaction:
Carbamate-Substituted Benzimidazole + Methylating Agent → Mebendazole
Uses:
Mebendazole is used to treat various roundworm infections, including ascariasis, trichuriasis, hookworm infections, and pinworm infections.
Side effects:
Common side effects include gastrointestinal disturbances (nausea, vomiting, diarrhea), headache, and dizziness. In rare cases, it may cause liver toxicity, bone marrow suppression, or hypersensitivity reactions.