Synthesis, Characterization and in silico Evaluations of Novel Chalcone Derivatives Containing Oxindole Ring

Abstract

In this study, a new series of chalcone derivatives containing an oxindole moiety to evaluate their physico-chemical properties, pharmacokinetic profiles and in silico biological potential. The designed derivatives 3a-d were obtained via a condensation reaction between 5-halo-isatin and substituted acetophenones using sodium ethoxide under moderate reaction conditions. The structures of the synthesized chalcone derivatives were confirmed using ¹H NMR, ¹³C NMR and HRMS. The in silico evaluations were performed using established database platforms, including SwissADME and admetLAB 3.0, to assess their absorption, distribution, metabolism, excretion and toxicity (ADMET) properties. All the compounds exhibited favourable drug-likeness, low predicted toxicity and compliance with Lipinski’s rule of five, suggesting their potential as orally active therapeutic agents. Molecular docking studies were also carried out to assess the binding affinities of compounds 3a-d against cancer-related target proteins such as PDGFRα (PDB ID: 9GZH) and VEGFR2 (PDB ID: 4ASD). Compounds 3b and 3d demonstrated the most promising binding energies (–11.973 and –7.726 kcal/mol, respectively), outperforming the reference drug, sunitinib. The docking results revealed key hydrogen bonding and hydrophobic interactions, offering insights into the stability of the compounds within the active sites of the target proteins.