IN-SILICO MOLECULAR DOCKING STUDIES, SYNTHESIS AND BIOLOGICAL EVALUATION OF NOVEL FURAN-AZETIDINONE HYBRIDS AS POTENTIAL ANTI-CANCER AGENTS

Furan and Azetidinone have been reported to possess various therapeutic activities, including anti-microbial and anti-cancer activity. Increasing drug resistance and high toxicity to the existing drugs have dictated the need to develop novel, effective agents with different scaffolds. With the perspective of identifying novel anti-cancer molecules, an approach was made to hybridize the different heterocyclic moieties. Thirtynovel Furan-Azetidinone hybrids were subjected to in-silico molecular docking studies to determine the novel molecules’ affinity for the anti-cancer targets. The four most promising derivatives were selected and synthesized based on docking scores. Condensation of ethyl cyanoacetate and o-toluidine at 160-190⁰C yielded 2-cyano-N-2(methylphenyl) acetamide (1). The reaction between (1) and benzoin yielded 2-amino-N-(2-methylphenyl) 4, 5-diphenylfuran-3- carboxamide (2). A series of Schiff bases ARJJ03 (1-2), were synthesized from (2) by refluxing it with various substituted aromatic aldehydes in ethanol using concentrated sulphuric acid as the catalyst. The title compounds ARJJ04 (1-2) were obtained by the cyclization of ARJJ03 (1-2) with Chloroacetyl chloride in 1, 4-dioxane in the presence of triethylamine. The synthesized derivatives were characterized by the UV, IR, NMR, and Mass spectral data. Investigation of in-vitro anti-cancer activity of compounds [ARJJ04 (1-2)] has been performed by MCF-7 cell line using MTT Assay.