Antimalarial Drug Mefloquine Strongly Inhibits PI3K (Phosphoinositide 3-kinase) and Exerts Anticancer Activity: A Literature based In Silico Study

Abstract

Mefloquine (MFQ) is an effective medication for the prevention and treatment of malaria. However, it has anticancer effects found in the literature. The main focus of this study is to review the anticancer activity of MFQ and also find the macromolecules or receptors that are mainly responsible for anticancer activity. For this reason, data was gathered (as of June 30, 2024) by utilizing a variety of reliable and well-known search engines. The molecular docking of MFQ with the selected macromolecules was performed. Our study findings showed that MFQ strongly showed anticancer activity by inhibiting proliferation, tumor growth, mitochondrial respiration, PI3K, MMP, IKK activation, Bcl-2, MCl-1, XIAP, and induced cell death, apoptosis, ROS, and PARP. In addition, an in silico study demonstrated that MFQ showed the highest binding affinity (–8.7 kcal/mol) against PI3K, whereas co-crystal ligand exhibited –8.6 kcal/mol binding affinity. The study also predicted that MFQ has better pharmacokinetics and toxicity parameters. However, we recommend additional evaluation and clinical research to further explore MFQ as a reliable PI3K inhibitor and an anticancer agent.