Anti-Tubercular and Anti-Inflammatory Activities of Azetidin-2-One Derivatives and Their Effects on the Activity of Phospholipase A2

The title compounds have been synthesized and tested for structure activity relationship for Phospholipase A2 (PLA2) [E.C. 3.1.1.4] enzyme inhibition. The in vitro anti-tubercular, PLA2 enzyme inhibitory activities of azetidin-2-one derivatives and in vivo anti-inflammatory studies using mice are highlighted. The analogues of azetidin-2-one were prepared based on the initial activity against Mycobacterium tuberculosis (Mtb). Certain azetidin-2-one analogues described herein showed moderate to good anti-tubercular activity. In particular, two compounds (4f) and (4g) exhibited MIC values of 1.56 and 0.78 μg/mL respectively against the Mtb H37Rv strain. Chloro substitution on aryloxy acid apparently enhanced the antimycobacterial activity and also PLA2 inhibition in the azetidin-2-one series described herein. The ability of azetidin-2-one analogues as anti-inflammatory agents has also been determined. The results show some correlation between anti-inflammatory, anti-tubercular activity and expression of PLA2 enzyme.