ENVIRONMENTALLY BENIGN SYNTHESIS, COMPUTATIONAL INVESTIGATION, AND MECHANISTIC STUDIES OF NOVEL COUMARIN-CARBONODITHIOATE FRAMEWORKS AS ANTICANCER DRUGS: AN APPROACH TO MICROWAVE SYNTHESIS
Suresh Sadashiv Kumbar, Kallappa Mahadevappa Hosamani*, Arun Kashivishwanath Shettar and Shrinivas D. Joshi
In the present study, an easy, rapid protocol for the synthesis of coumarin-carbonodithioate frameworks (1a-1j) under microwave (MW) irradiation and conventional method is described. Further, the efforts underwent towards the development of MW assisted protocol, through which the yields of the compounds were improved drastically in shorter reaction time. The new compounds are characterized by IR, 1H, 13C-NMR, Mass and Elemental analyses. Computational experiments were carried out in order to study the interactions between coumarins and Bcl-2 protein showed promising activity. Amongst, the compounds 1a, 1c, 1d, 1f, 1h, and 1j have been selected for NCI-60 One-Dose screening for their in-vitro anticancer activities and displayed excellent growth inhibition. The Structure-Activity Relationship studies explicated the obtained results. The title compounds analyzed for their physicochemical properties set by Lipinski rule and found that none of the compounds violated the rule and fall well in the range of Rule of five [RO5].
Keywords: MW irradiation, computational studies, anticancer activity, SAR studies.
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