Synthesis and evaluation of novel coumarin-oxime ethers as potential anti-tubercular agents: Their DNA cleavage ability and BSA interaction study

As a contribution to the development of novel coumarin-oxime ether conjugates with therapeutically interesting properties, a series of coumarin-oxime ether (1a-1j) was synthesised using S N 2 reaction of bromomethyl coumarins with butane-2,3-dione monoxime. Invitro anti-tuberculosis activityagainstMTBH 37 Rv strain was established for the coumarin-oxime ether (1a-1j). Most of the compounds exhibited significant activity with minimum inhibitory concentration (MIC)in the range of 0.04-3.12 μg mL -1 . Compound (1h) was identified as a hit candidate exhibiting MIC of 0.04 μg mL -1 , closer to the MIC value of Isoniazid (0.02 μg mL -1 ), a commercially available drug for the treatment of tuberculosis. Compound 1h also displayed a low level of toxicity in Vero cells along with a good safety profile in vitro. Compounds that showed potent anti-tubercular activity were also found to cleave DNA more efficiently and thereby exhibit nuclease activity. The most active compound (1h) was further studied to deduce the mode of interaction with model serum protein, bovine serum albumin (BSA).