Abstract
Cancer has emerged as a global concern because it affects a larger population and is a major cause of death worlwide. Despite advancements in medical technologies and cancer therapy, there is still a need for effective therapeutics. The development of new drug molecules is tedious, expensive, and laborious process that can take years to reach in clinical trials. In recent years, drug repurposing has gained popularity because it accelerates the process of drug discovery. We propose that antimalarial drug artemisinin (AMS) be repurposed in anticancer therapeutics. AMS can potentially alter major signaling pathways involved in cancer, including Wnt/b-catenin and PI3K signaling pathways. Pyruvate dehydrogenase kinase 3 (PDK3) is overexpressed in many cancer types, involved in these signaling and being considered as an attractive drug target for cancer therapy. The current study investigated the binding and PDK3 inhibitory potential AMS using combined computational and spectroscopic methods. We observed a significant binding affinity of AMS for PDK3. In addition, the kinase activity of PDK3 is significantly inhibited by AMS. We further complemented our findings with molecular docking and 100 ns MD simulation studies. We propose that AMS may be explored as a possible anticancer agent after getting the required clinical validation. (c) 2022 Elsevier B.V. All rights reserved.