Isoniazid, Mechanism of action, Biological Activity, Resistance and Biotransformation

Abstract

Isoniazid is a synthetic antimicrobial and one of the most essential first-line drugs used in the treatment of tuberculosis. In addition, isoniazid has been used as a prophylactic drug for patients with latent Mycobacterium tuberculosis infection to prevent the reactivation of the disease. It is a prodrug that is activated by catalase-peroxidase (KatG) enzyme. Catalase peroxidase enzyme converts isoniazid to reactive species. Isoniazid reactive species inhibit enoyl acyl-carrier-protein reductase (InhA) enzyme, which is involved in the biosynthesis of fatty acids of mycobacteria. Isoniazid is metabolized by amidase enzyme into isonicotinic acid and hydrazine. Chronic toxicity of isoniazid results in hepatotoxicity and peripheral neuropathy. For active tuberculosis, isoniazid is often used together with rifampicin, pyrazinamide, and either streptomycin or ethambutol. Multiple extensively and totally drug-resistant strains of Mycobacterium tuberculosis were reported. Due to the development of Mycobacterium tuberculosis resistance to isoniazid, a continuous search for new drugs is a demand to combat this global problem.