Synthesis of New Series of Benzimidazole Acetic Acid Derivatives Bearing Thiophene Moiety for Anti-Tubercular Activity

Abstract

Tuberculosis is a disease that has been known from the earliest of recorded history. The development of the multidrug-resistant TB (Mtb) strains, treatment of active TB is more complicated than it used to be. Therefore, there is an urgent need for the development of novel anti-tuberculosis drugs, which will be active against both drug-sensitive and drug-resistant Mtb strains. FtsZ (Filamental temperature-sensitive protein Z), a tubulin homolog, is the most critical protein for bacterial cell division. GTP dependent polymerization of FtsZ forms a dynamic helical structure at the center of the cell called Z-ring. Recruitment of other cell division proteins leads to the contraction of Z-ring, which initiates the cell division. Therefore, novel molecules, which interfere polymerization or depolymerization of FtsZ can be developed as anti-tuberculosis agents. It has been found that the treatment of MTB with albendazole and thiabendazole, known tubulin inhibitors, leads to the cell filamentation, indicative of FtsZ inhibition. Accordingly, we designed and synthesized a library of benzimidazoles to investigate their microbacterial activities. A number of these compounds demonstrated substantial activity against H37RV strain. We will present the synthesis and biological evaluations of these compounds.