High-Throughput Virtual Screening with Molecular Docking, Pharmacophore Modelling and ADME Prediction to Discover Potential Inhibitors of Plasmodium falciparum Lactate Dehydrogenase (PfLDH) from Compounds of Combretaceae Family

Babatunde B. Samuel1*, Wande M. Oluyemi1, Titilayo O. Johnson2, Abayomi E. Adegboyega2

1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ibadan, Nigeria

2Department of Biochemistry, Faculty of Medical Sciences, University of Jos, Nigeria



Corresponding Author: bb.samuel@mail.ui.edu.ng; Tel: +234-813-195-1725
Recieved Date: 07 April 2021; Accepted Date: 10 September 2021; Published Date: 4 October
Citation: Samuel BB, Oluyemi WM, Johnson TO, Adegboyega AE. High-Throughput Virtual Screening with Molecular Docking, Pharmacophore Modelling and ADME Prediction to Discover Potential Inhibitors of Plasmodium falciparum Lactate Dehydrogenase (PfLDH) from Compounds of Combretaceae Family. Trop J Nat Prod Res. 2021; 5(9):1665-1672. http://www.doi.org/10.26538/tjnpr/v5i9.22
Copyright:
© 2021 Samuel et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Visit for more related articles at  Tropical Journal of Natural Product Research




ABSTRACT

The increased prevalence of malaria requires continuous efforts towards the discovery of natural antimalarial agents targeting important biochemical pathways of the parasite. The Plasmoduim falciparum lactate dehydrogenase (pfLDH) is a glycolytic enzyme whose critical roles and unique characteristics make it an efficient antimalarial target. The aim of this study was to employ in silico methods to identify potential inhibitors of pfLDH from the selected bioactive compounds of Combretaceae species. One hundred and fifty (150) Combretaceae compounds were screened using molecular docking analysis on Schrödinger Maestro 12.5, followed by pharmacophore modelling and ADMET (absorption, distribution, metabolism, excretion and toxicity) study of the highest affinity compounds. Myricetin 3-O-glucoside and 2-O-Galloylisovitexin showed higher binding affinities (-13.413 Kcal/mol and -12.896 Kcal/mol respectively) for pfLDH compared with -10.400 Kcal/mol displayed by nicotinamide adenine dinucleotide (NADH) (the co-factor). They interacted with GLY27, GLY29, MET30, ILE31, ASP53, GLY99, THR101 and TYR247 at the NADH binding site of the enzyme. The pharmacophore modelling showed the involvement of aromatic rings and hydrogen bond donors and acceptors in the interactions of the compounds with the target. Hence, these compounds could be said to possess the structural features, binding affinities and molecular interactions required as inhibitors of pfLDH and could be developed into antimalarial drugs following lead optimisation and experimental studies.

Keywords: <span style="font-size:10.0pt;line-height:107%;font-family:"Tahoma",sans-serif;mso-fareast-font-family:Calibri;mso-fareast-theme-font:min
Back to Articles

ISSN: 2616-0684 (Print)
ISSN: 2616-0692 (Online)
DOI: 10.26538/tjnpr
Index Copernicus Value (ICV) for 2017: 59.83
Scopus citescore 0.3 (2020)

Indexing & Abstracting

citescore 0.3 (2020)

j-gate logo

International Innovative Journal Impact Factor

African Index Medicus

CAS

Index Copernicus International

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License

Crossref Content Registration logo

WorldCat Discovery Service

Geneva Foundation for Medical Education and Research