Synthesis, in vitro, and in silico studies of novel poly‐heterocyclic compounds bearing pyridine and furan moieties as potential anticancer agents

Abstract

Thirteen novel poly‐heterocyclic compounds containing pyridine and furan moieties were synthesized and fully characterized by 1H NMR, 13C NMR, FTIR, and elemental analysis. The optimized geometry of the most stable conformation of the synthesized compounds was determined at the DFT/B3LYP level of theory. Frontier molecular orbitals, molecular electrostatic potential, and atoms in molecules analysis were performed to better understand the electronic properties, reactivity, and intermolecular interactions. The cytotoxicity of all compounds was assessed In vitro against MCF-7 and A-2780 cell lines using the MTT assay. Among them, compounds 2c, 3c, 3d, 4a, and 4c at 0.1 µM concentration showed more potent cytotoxicity against the MCF-7 cells than the reference drug docetaxel. On the other hand, compounds 2c, 3a, 3c, and 4c are more cytotoxic against the A-2780 cell line compared to the standard at the same concentration. The docking studies revealed an excellent affinity for the active site of the human topoisomerase-IIβ enzyme, which may explain the promising cytotoxicity of these classes of molecules. The in silico evaluation of ADMET parameters indicated good pharmacokinetic properties of all the investigated compounds.