Molecular docking study and ADME properties of isoquinoline and benzazecine derivatives

Abstract

Azecines containing an allene fragment, typically consisting of 8-11 membered rings, are found in both natural products and synthetic compounds with a wide range of biological activities. Our previous study reported the synthesis of 6-perfluoroalkyl substituted allene benzazecines. Evaluation of their in vitro cytotoxicity against Hep-G2, MCF-7, A549, and KB cancer cell lines showed promising results. Among eighteen synthesized compounds, two potential anticancer candidates were identified due to their low IC₅₀ values. In the present study, molecular docking simulations were employed to investigate the binding modes of these active isoquinoline and benzazecine derivatives with the vascular endothelial growth factor receptor (VEGFR). Binding energies, molecular orientations, and interactions between the compounds and the target protein were analyzed. In addition, drug likeness and in silico ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties were evaluated to provide insights into the structure activity relationship.