Hemchandra K. Chaudhari*, Afsar A. Siddikia and Yogesh D. Manohara Pages 318 - 325 ( 8 )
Background: Coumarins, possesing antimicrobial activity are often used by the researchers to develop novel synthetic and semisynthetic coumarin based therapeutic agents. Molecular hybridization concept was used to design coumarin hybrid molecules. Synthesized molecules were evaluated for their invitro antibacterial activities. We designed Coumarin derivatives of diphenyl ether and oxadiazole. Most of the compounds showed antimicrobial activity against gram-positive as well as gram-negative bacteria.Methods: ADME properties of the molecules calculated by Qikprop program. It predicts both physically appropriate descriptors and drug like properties. Oxadiazole and diphenyl ether hydrazone derivatives of coumarin were designed by molecular hybridization concept. Designed molecules were synthesized and confirmed by spectral data; further synthesized molecules were screened for antimicrobial activity by using the REMA plate method. Results: We analyzed drug like properties with 44 physically relevant descriptors of coumarin derivatives by Qikprop, out of 28 ligands 14 all coumarin-oxadiazole derivatives structures exhibited allowed values for the properties analyzed and exhibited drug-like characteristics derived from Lipinski’s rule of 5. Biological screening of coumarin-oxadiazole derivative of nitrophenyl 8g was active against both gram positive and negative bacteria. It was seen that electron withdrawing substituent such as nitro group was important for activity. For coumarin -diphenyl hydrazone derivatives, halogens chloro substituent also exhibited significant activity as compare to fluoro substituted compounds. The most active hydrazone derivatives were 6c and 6g with chloro and trifluoromethoxy substitution on benzene ring. In part B, fluoro substitution at aromatic ring had no effect on improvement of antibacterial activity. However it showed that electron withdrawing group were more active and exhibited significant improvement in the antibacterial activity. Conclusion: The efficient and instructive SAR study will provide deeper insight into further optimization of coumarin-oxadiazole and coumarin-diphenyl ether derivatives representing to promising leads for further exploration as antibacterial agents.
Antibacterial, coumarin, diphenyl ether, oxadiazole, hydrazide, molecular hybridization, qikprop.
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N.P. Marg, Matunga (E), Mumbai-400019, Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Matunga, Mumbai-400 019, Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Matunga, Mumbai-400 019