Benzo[d]thiazole-2-carboxamides as new antituberculosis chemotypes inhibiting mycobacterial ATP phosphoribosyl transferase.

Abstract

Aims: The screening of antimycobacterial benzo[d]thiazole-2-carboxamides against ATP-phosphoribosyl transferase (ATP-PRTase) was conducted. Materials & methods: The antitubercular potential of compounds1 and 2 against ATP-PRTase was assessed through the determination of half maximal effective concentration (EC50) andbinding constant (Kd), as well ascompetitive inhibitory studies and studies of perturbation of secondary structure, molecular modelingand L-histidine complementation assay. Results & conclusion:Compounds 1n and 2a significantly inhibited ATP-PRTaseas evidenced by their EC50 and Kdvaluesand the perturbation of thesecondary structure study. Compound 1n exhibitedstronger competitive inhibition toward ATP compared with 2a. The inhibition of the growth of Mycobacterium tuberculosis by targeting the L-histidine biosynthesis pathway and molecular modeling studies further supported theinhibition of ATP-PRTase.