Predicting Plasmodium falciparum kinase inhibitors from antimalarial medicinal herbs using computational modeling approach

Temitope Isaac Adelusi; Taiwo Ooreoluwa Ojo; Olawale Quadri Bolaji; Moyosoluwa Precious Oyewole; Olamide Tosin Olaoba; Elijah Kolawole Oladipo

doi:10.1007/s40203-023-00175-z

Predicting Plasmodium falciparum kinase inhibitors from antimalarial medicinal herbs using computational modeling approach

In Silico Pharmacol. 2023 Dec 19;12(1):4. doi: 10.1007/s40203-023-00175-z. eCollection 2024.

Authors

Temitope Isaac Adelusi¹, Taiwo Ooreoluwa Ojo^{1

2}, Olawale Quadri Bolaji¹, Moyosoluwa Precious Oyewole¹, Olamide Tosin Olaoba³, Elijah Kolawole Oladipo^{2

4}

Affiliations

¹ Computational Molecular Biology and Drug Discovery Laboratory, Department of Biochemistry, Ladoke Akintola University of Technology, P.M.B 210214, Ogbomoso, Oyo State Nigeria.
² Genomics unit, Helix Biogen Institute, P.M.B 212102, Ogbomoso, Oyo State Nigeria.
³ Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO 65211 USA.
⁴ Laboratory of Molecular Biology, Bioinformatics and Immunology, Department of Microbiology, Adeleke University, Ede, Osun State Nigeria.

PMID: 38130691
PMCID: PMC10730500 (available on 2024-12-19)
DOI: 10.1007/s40203-023-00175-z

Abstract

Malaria remains a significant public health challenge, with resistance to available drugs necessitating the development of novel therapies targeting invasion-dependent proteins. Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK-1) is essential for host erythrocyte invasion and parasite asexual development. This study screened a library of 490 compounds using computational methods to identify potential PfCDPK-1 inhibitors. Three compounds; 17-hydroxyazadiradione, Picracin, and Epicatechin-gallate derived from known antimalarial botanicals, showed potent inhibitory effects on PfCDPK-1. These compounds exhibited better binding affinities (-8.8, -9.1, -9.3 kCal/mol respectively), pharmacokinetics, and physicochemical properties than the purported inhibitory standard of PfCDPK-1, Purfalcamine. Molecular dynamics simulations (50 ns) and molecular mechanics analyses confirmed the stability and binding rigidity of these compounds at the active pocket of PfCDPK-1. The results suggest that these compounds are promising pharmacological targets with potential therapeutic effects for malaria treatment/management without undesirable side effects. Therefore, this study provides new insights into the development of effective antimalarial agents targeting invasion-dependent proteins, which could help combat the global malaria burden.

Supplementary information: The online version contains supplementary material available at 10.1007/s40203-023-00175-z.

Keywords: Malaria; Molecular docking; Molecular simulation; PfCDPK1; Plasmodium falciparum; Virtual screening.

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