Design, synthesis, and evaluation of antitubercular activity of a novel benzothiazole-containing an azetidinone ring

Abstract

Recent studies have demonstrated that 2-amino-substituted benzothiazole derivatives exhibit significant antitubercularactivity. In this study, new compounds of benzothiazole-containing azetidinone derivatives were designed and synthesizedusing substituted benzaldehydeN-(5fluoro-1,3-benzothiazol-2-yl) semicarbazone, chloroacetyl chloride, and triethylaminein DMF. The structures of the synthesized compounds were characterized by TLC, IR, elemental analysis, and 1H NMR. Invitro screening data revealed that all the designed and synthesized compounds A6–A10 exhibited the ability to inhibit thegrowth of Mycobacterium tuberculosis in terms of MIC. Variable and modest activity was observed against the investigatedstrains of bacteria; however, the compound A6 exhibited significant antitubercular activity against M. tuberculosis H37Rv(MTCC 200) compared to that of the reference drugs isoniazid and rifampicin. These experimental data were consistentwith our computational predictions in terms of the compound A6 that exhibited a satisfactory backbone for the antitubercularactivity, perhaps due to an increase in hydrophobicity resulting in better penetration through the cell wall of M.tuberculosis.