Goniothalamin and Its Analogues as Potential Inhibitors of Plasmodium falciparum Lactate Dehydrogenase Enzyme: Molecular Docking, Molecular Dynamics Simulation Studies, and Pharmacokinetics Analysis

• Published in: Malaysian Journal of Chemistry
• Main Author: Ideris S.; Imran S.; Latip N.A.; Osman C.P.
• Format: Article
• Language: English
• Published: Malaysian Institute of Chemistry 2024
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85186976547&doi=10.55373%2fmjchem.v26i1.27&partnerID=40&md5=35baa315b5a939543b88988f69a87c50

Malaria has been a major concern worldwide due to the resistance of malarial parasites to most of the available antimalarial drugs. Therefore, developing new drugs is necessary to overcome this drug resistance. Plasmodium falciparum lactate dehydrogenase (pfLDH) is a gene necessary for the survival of plasmodium parasites and is a potential antimalarial target. Our objective was to discover goniothalamin and its twenty-nine analogues as potent antimalarial molecules with pfLDH inhibitory activity effective against resistant strains of plasmodium parasites. The molecular docking studies of the compounds were performed by AutoDock 4.2. The interaction of ligands and receptor bindings was visualized by Discovery Studio Visualizer 4.0. The Molecular dynamics simulation was carried out using Desmond v.2018. Pharmacokinetics Analysis of the compounds was done using Molinspiration tools and the pKCSM server. Molecular docking analysis showed that compounds 3,5-dimethoxy goniothalamin (-6.29 kcal/mol), parvistone (-6.22 kcal/mol), and 8-acetylgoniotriol (-6.19 kcal/mol) exhibited higher binding energy than existing drugs of chloroquine (-6.11 kcal/mol) against pfLDH protein. Further, these compounds show multiple interactions with the active sites of the pfLDH protein. In addition, these compounds fulfill the drug-likeness properties and pass the ADMET prediction. The results from the molecular dynamics simulations indicate that the 3,5-dimethoxy goniothalamin shows promising inhibitors towards pfLDH protein. The results showed that the selected compounds exhibit promising antimalarial activities, which are crucial considerations in drug design and development. © 2024 Malaysian Institute of Chemistry. All rights reserved.