InhA Inhibitors as Potential Antitubercular Agents (A Review)

Infectious diseases pose a potential threat and are responsible for killing more people globally than any other single cause. For six decades, antibiotics have been a bulwark against bacterial infectious diseases. This bulwark is failing due to the appearance of resistant bacterial strains. The biosynthesis pathway of fatty acids in bacteria represents a validated target for antibacterial drug discovery, although it is still relatively unexplored. Bacterial FAS-II is essential for survival of bacterial cells, furthermore as it is distinct from FAS-I pathway in mammals, it constitutes a rational beginning point for the design of novel anti-infective drugs. Tuberculosis (TB) is a potentially serious infectious disease. Several strategies that have been adopted for the development of new therapeutic agents against the strains of tuberculosis which are drug resistant involve not only the design and synthesis of compounds against earlier known targets but also the identification and inhibition of novel drug targets. Isoniazid (INH), the first-line agent used for prevention and treatment of tuberculosis targets the enoyl reductase (InhA) enzyme in fatty acid biosynthesis pathway of the mycobacteria. KatG, is the enzyme which activates isoniazid and mutations in this enzyme lead to the majority of INHresistant clinical strains. Thus only those compounds will work against most of the INH resistant strains of mycobacteria which do not require activation of KatG for InhA inhibition.