Molecular Docking, Drug-likeness, and ADMET Predictions for Goniothalamin and its Analogues as Plasmepsin II Inhibitors

• Published in: Malaysian Journal of Chemistry
• Main Author: Ideris S.; Imran S.; Abd Latip N.; Osman C.P.
• Format: Article
• Language: English
• Published: Malaysian Institute of Chemistry 2024
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85190864128&doi=10.55373%2fmjchem.v26i2.33&partnerID=40&md5=3066848edce7462f7c1265f3634ff268

Malaria is a life-threatening disease caused by the Plasmodium parasite, which is transmitted to humans through the female Anopheles mosquito. Plasmepsin II is an essential digestive component in the parasite's food vacuole protease involved in haemoglobin degradation. Our objective was to evaluate goniothalamin and its analogues as potent antimalarial molecules with plasmepsin II inhibitory activity effective against resistant strains of Plasmodium parasites. A molecular docking approach was applied to identify plausible binding interactions between goniothalamin derivatives and plasmepsin II. Based on molecular docking analysis, we found that goniotriol, goniodiol, 8-acetylgoniotriol, trifluoromethyl howiinol, and parvistone formed conventional hydrogen bonds with the catalytic dyad Asp34 and Asp214 within the active site of plasmepsin II. In addition, these compounds passed the ADMET prediction test and fulfilled Lipinski's rule of five. The results of this study can be used to identify, optimize and understand goniothalamin and its analogues as potential drug candidates to accelerate the path from initial drug discovery to successful clinical application for malaria. © 2024 Malaysian Institute of Chemistry. All rights reserved.