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 polymeriza¬tion or depolymerization of FtsZ can be developed as anti-tuberculosis agents. It has been found that the treat¬ment 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 benzimida¬zoles 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.