Synthesis, anticancer evaluation and molecular docking studies of 2,5-bis(indolyl)-1,3,4-oxadiazoles, Nortopsentin analogues

A series of ten novel 2,5-bis(indolyl)-1,3,4-oxadiazoles were designed and synthesized. All these compounds were evaluated for their cytotoxicity against four cancer cell lines namely A549, MDA-MB-231, MCF-7 and HeLa using MIT reduced assay. Among them, compound 12e exhibited good cytotoxicity on MCF-7 cell line with IC50 value of 1.8 mu M and it was identified as a promising drug lead when compared to the standard drug doxorubicin (IC50 value 0.98 mu M). Compound, 12h exhibited better antitumor activity against three cancer cell lines i.e., lung (A549), breast (MCF-7) and cervical (HeLa) with IC50 values of 3.3 mu M, 2.6 mu M and 6.34 mu M respectively. The impact of these compounds on colchicine binding site of tubulin polymer was carefully investigated using molecular docking studies and interpretations between actives and inactive were explained. (C) 2020 Published by Elsevier B.V.