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

• Published in: In silico pharmacology Vol. 12; no. 1; p. 4
• Main Authors: Adelusi, Temitope Isaac, Ojo, Taiwo Ooreoluwa, Bolaji, Olawale Quadri, Oyewole, Moyosoluwa Precious, Olaoba, Olamide Tosin, Oladipo, Elijah Kolawole
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 2024; Springer Nature B.V
• Subjects: Antiparasitic agents; Binding; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Cellular and Medical Topics; Computational Science and Engineering; Dynamic stability; Herbal medicine; Identification methods; Kinases; Malaria; Medicinal Chemistry; Medicinal herbs; Molecular dynamics; Original Research; Pharmacology/Toxicology; Physiological; Proteins; Public health; Side effects; Stability analysis; Molecular simulation; Virtual screening; Malaria; CDPK1; Molecular docking; Plasmodium falciparum; PfCDPK1
• ISSN: 2193-9616; 2193-9616
• DOI: 10.1007/s40203-023-00175-z

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.