In silico Drug Repurposing of FDA-Approved Artemisinins as Potent Chemotherapeutics Targeting Bcl-2, CDK-6 & VEGFR-2: Density Functional Exploration and Molecular Docking Study

Abstract

The strategy of using existing drugs originally developed for one disease to treat other indications has found success across medical fields. This paper focuses on drug repurposing of artemisinin and its derivatives (artenimol, artemether, artemotil, and artesunate) that kill malaria parasites for anticancer agents, specifically targeting Bcl-2, CDK-6, and VEGFR-2. The Artemisinins 1-5 were analyzed for compliance with Lipinski’s drug-likeness rule and optimum ADME parameters. The results of which revealed all calculated physicochemical descriptors and pharmacokinetic properties are within the expected thresholds. Toxicity in terms of predicted median lethal dose (LD50) in mg/kg weight of investigated Artemisinins 1-5 is also reported. Artemisinins 1-5 were subjected to molecular docking and Density Functional Theory (DFT) analysis to discern their molecular interactions at the active site of Bcl-2, CDK-6, and VEGFR-2. The molecular docking study revealed that Artemisinins 1-5 were able to target CDK-6 and VEGFR-2. DFT/B3LYP theoretical calculations for optimization, DFT, frequency, and HOMO/LUMO were performed to obtain electronic and structural properties, chemical reactivity descriptors. Hence, these findings will be highly beneficial in optimizing the utility of the development of Artemisinins 1-5 for cancer therapeutics, specifically targeting CDK-6 and VEGFR-2.