مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
Computational screening of artemisinin-based compounds as multi-target inhibitors of key atherogenic proteins
Computational screening of artemisinin-based compounds as multi-target inhibitors of key atherogenic proteins
Shima Zarinfard,1,*Zahra Zarinfar,2Maryam Musavi,3Amir Abbas Momtazi-Borojeni,4
1. Departments of Medical Biotechnology, School of Medicine, Neyshabur University of Medical Sciences, Neyshabur, Iran 2. Departments of Medical Biotechnology, School of Medicine, Neyshabur University of Medical Sciences, Neyshabur, Iran 3. Assistant Professor of Medical Biotechnology, Neyshabur University of Medical Sciences, Neyshabur, Iran 4. Assistant Professor of Medical Biotechnology, Neyshabur University of Medical Sciences, Neyshabur, Iran
Introduction: Atherosclerosis is a progressive inflammatory disease caused by lipid dysregulation and accumulation of atherogenic lipoproteins. Key proteins such as ApoB-100, CETP, PCSK9, and Lipin-1 play central roles in its pathogenesis. Artemisinin and its derivative artesunate, traditionally used as antimalarial agents, have recently shown anti-inflammatory and cardiovascular protective properties, suggesting potential for repurposing.
Objectives:
This study aimed to investigate the multitarget inhibitory potential of artemisinin and artesunate against atherogenic proteins through computational docking and ADMET analyses.
Methods: Crystal structures of ApoB-100 (PDB: 9BD8), CETP (4EWS), PCSK9 (6U26), and Lipin-1 (7KIL) were retrieved from the Protein Data Bank. Molecular docking simulations were performed using AutoDock Vina, with pose clustering and replicate runs to assess reproducibility. Validation was achieved by re-docking co-crystallized ligands (RMSD ≤ 2.0 Å). Pharmacokinetic and ADMET properties were predicted using SwissADME.
Results: Artemisinin exhibited stronger binding affinities compared with Artesunate for most protein targets (CETP, Lipin-1, and PCSK9), whereas Artesunate showed slightly better binding only toward ApoB-100. Docking results were robust, with low standard deviations (≤ 0.3 kcal/mol) and acceptable RMSD values. ADMET profiling indicated favorable drug-likeness, good oral bioavailability, and no major violations of Lipinski’s rules.
Conclusion: Artemisinin demonstrates promising multitarget inhibitory activity against atherogenic proteins, highlighting its potential as a repurposed therapeutic candidate for atherosclerosis management. Further validation through molecular dynamics simulations and experimental studies is recommended.