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 antitubercular activity. In this study, new compounds of benzothiazole-containing azetidinone derivatives were designed and synthesized using substituted benzaldehydeN-(5fluoro-1,3-benzothiazol-2-yl) semicarbazone, chloroacetyl chloride, and  triethylamine in DMF. The structures of the synthesized compounds were characterized by TLC, IR, elemental analysis, and 1H NMR. In vitro screening data revealed that all the designed and synthesized compounds A6–A10 exhibited the ability to inhibit the growth of Mycobacterium tuberculosis in terms of MIC. Variable and modest activity was observed against the investigated strains 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 consistent with our computational predictions in terms of the compound A6 that exhibited a satisfactory backbone for the antitubercular activity, perhaps due to an increase in hydrophobicity resulting in better penetration through the cell wall of M. tuberculosis.

Keywords

• Benzothiazole
• azetidinone
• Mycobacterium tuberculosis
• synthesis

References

1. Patel VR, Patel CN, Sen DJ (2011). Synthesis and Biological evaluation of some 5-[(substituted)-Phenyl]-3-(4-Chlorophenyl)-4,5-Dihydro-1H-Pyrazole-1 Carbathiomide Derivatives. Internationale Pharmaceutica Sciencia 1(1): 133-136.
2. Sarkar S, Pasha TY, Shivakumar B, Reddy VM (2008). Synthesis and Evaluation of Antibacterial and Antiinflammatory Activity of 7-Alkyl/Aryl amino-6-fluoro-2- phenyl Carboxamido-1,3-benzothiazoles. Asian J Chem 20(4): 3227-3230.
3. Sarkar S, Pasha TY, Shivakumar B, Chimkode R (2008). Synthesis of benzothiazole derivatives and study of their anti-fungal activities. Oriantal J Chem 24(2): 705-708.
4. Sarkar S, Pasha TY, Shivakumar B, Chimkode R (2008). Synthesis of new 7-alkyl /aryl amino –6-fluro 2 substituated phenyl carboxamido (1,3 ) benzothiazoles as anthelmintic agents. Indian J Heterocycl. Chem 24(7): 383-388.
5. Sarkar S (2011). Synthesis and Pharmacological evaluation of New 7 alkyl/ aryl amino-6-fluro 2- (3 nitro phenyl) Carboxamido (1,3)benzothiazole as anthelmintic agents. J Pharm Res 1(12): 4599.
6. Sarkar S, Dwivedi J, Chauhan R (2013). Synthesis and biological activity of novel azetidinone and thiazolidinone starting from benzothiazole. Ind J Heterocyclic Chem 23: 75-80.
7. Sarkar S, Dwivedi J, Chauhan R (2013). Synthesis of 1-[2 (substituted phenyl)-4-oxothiazolidin-3-yl]-3-(6-fluro-7-chloro-1,3-benzothiazol-2-yl)-ureas as anthelmintic agent. J Pharm Res 5(7): 439-442.
8. Sarkar S (2017). Synthesis and antimicrobial activity of Some azetidinone derivatives Containing Substituted Benzothiazole. Indian J Heterocycl. Chem 69(1): 46-50.