In silico investigation of the binding interaction between steroidal drugs and HMG CoA reductase for cancer treatment

Jacob, Blessy and Tarun, B.L and Chandy, Vineeth (2025) In silico investigation of the binding interaction between steroidal drugs and HMG CoA reductase for cancer treatment. World Journal of Biology Pharmacy and Health Sciences, 23 (1). pp. 414-422. ISSN 2582-5542

The enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) serves as the rate-limiting catalyst in cholesterol synthesis and has gained attention as a potential target in cancer therapy due to its involvement in cellular proliferation and survival pathways. In this work, an in silico analysis was conducted to examine the binding interactions of various steroidal drugs with HMG-CoA reductase to assess their anticancer potential. Molecular docking was performed using AutoDock Vina to evaluate binding energies, hydrogen bond formation, and the specific amino acid residues involved in the interactions, providing insights into the stability of the drug-enzyme complexes. The findings revealed that the steroidal drugs demonstrated strong binding affinities at the enzyme’s active site, engaging key catalytic residues similar to those targeted by standard anticancer drugs. Additionally, SwissADME was employed to predict the ADME properties and drug-likeness of the steroidal compounds, indicating that they possess favorable pharmacokinetic characteristics for oral administration. Overall, these results suggest that steroidal drugs could act as inhibitors of HMG-CoA reductase, potentially exerting anticancer activity by disrupting cholesterol biosynthesis in rapidly dividing cancer cells. Further in vitro and in vivo studies are necessary to validate these findings and to explore the repositioning of these steroidal drugs within cancer treatment strategies.