Benzofuran-3(2H)-Ones Derivatives: Synthesis, Docking and Evaluation of Their in Vitro Anticancer Studies

We reported the synthesis of novel benzofuran-3(2H)-ones derivatives (3a-n) and their binding affinity study was done with the progestrone and estrogen receptor proteins. The program AUTODOCK4.2 was used for a critical part of model building through conformational sampling of docking poses within the Progestrone receptor/Estrogen receptor (PR/ER) binding pocket. The binding energy (B.E.) or unsubstituted benzofuran-3(2H)-one (aurone) was obtained −5.43 kcal/mol; however, diversely substituted benzofuran-3(2H)-one 3a showed much higher binding energy (−11.07 kcal/mol) for ligand-progesterone receptor-binding complex (PDB code: 1ZUC) with Ki = 7.68 nM. We also observed the effects of alkyl chain and aromatic ring substitutions at C2-position in benzofuranone moiety on the basis of their interaction with ER/PR. The synthesized compounds were investigated for their anticancer activity also. Among the synthesized molecules, some compounds showed remarkable in vitro anticancer activity against the human breast cancer cells. It was observed that hydrophobic interaction was increased due to introduction of alkyl chain and aromatic ring at C2-position in the synthesized compounds and so enhanced the anti-proliferative activities.