Research Article

In Silico Evaluation of Pharmacokinetic Properties and Drug Likeness of Statins Targeting Histone deacetylase

Abstract

Drug repurposing holds great potential in terms of discovering new anticancer agents via assigning new therapeutic uses to already approved drugs. Through epigenetic regulation of gene expression, histone deacetylase 3 (HDAC3) functions with great importance in the progression of breast cancer making it an attractive molecular target. We report a full in silico profiling of selected statins (Atorvastatin, Fluvastatin, Pitavastatin, Pravastatin, and Rosuvastatin) as potential HDAC inhibitors compared to the Histone deacetylase 3 crystal structure (PDB ID: 4LXZ) and reference inhibitor Vorinostat. Molecular docking results reveal that all of the evaluated statins dock in the HDAC catalytic pocket and interact with the catalytic Zn2 + ion. Atorvastatin showed the best binding affinity (-10.93 Kcal.mol– 1) followed by Vorinostat (-8.51 Kcal.mol– 1) and stable metal coordination most likely hydrogen bonding and series of π–π interactions with the active-site residues. Structure–activity relationship analyses revealed that both hydrophobic surface area, aromatic moieties and accessibility of the carboxylate zinc-binding group have a major effect on binding stability. Full ADMET profile showed good pharmacokinetic characteristics for most statins, with high predicted absorption from the gut, moderate distribution, amenable metabolic profiles, and generally acceptable toxicity predictions, although atorvastatin showed possible AMES positivity and hERG II inhibition. These computational studies indicate that statins appear to act as very weak non-classical HDAC inhibitors, especially Atorvastatin, consistent with the concept of repurposing these drugs as possible epigenetic anticancer agents. 

Keywprds: Drug repurposing, Statins, Histone deacetylase 3, Vorinostat, Molecular docking, Structure activity relationship (SAR), ADMET prediction, Pharmacokinetic profiling.

Authors affiliation:

Mohammed Zuheir Hassan: Department of Aesthetic and Laser Techniques, College of Health and Medical Technology, University of Alkafeel, Najaf, Iraq.
Ahmed Ridha Abduljawad (ORCID): Faculty of Medical Technologies, Islamic University, Najaf, Iraq.
Jawad Kadhim Alshams: College of Pharmacy, University of AlKafeel, Najaf, Iraq.
Dhurgham Qasim Shaheed: College of Pharmacy, University of AlKafeel, Najaf, Iraq & ARCPMS University of AlKafeel, Najaf, Iraq.
Ali Jabbar Radhi (ORCID)*: College of Pharmacy, University of AlKafeel, Najaf, Iraq & ARCPMS University of AlKafeel, Najaf, Iraq.

How to Cite: M.Z. Hassan, A.R. Abduljawad, J.K. Alshams, D.Q. Shaheed and A.J. Radhi. In Silico Evaluation of Pharmacokinetic Properties and Drug Likeness of Statins Targeting Histone deacetylase. Current Research in Health Sciences, 4(1):24–33, 2026. https://doi.org/10.58613/crhs415