Glucosyl Xanthone, d-Idopyranoside, Fatty Acid and Isoprene Derivatives as New Anti-Malarial Compounds Targeting <i>Plasmodium Falciparum</i> Thymidine Monophosphate Kinase (PfTMPK)

Background Chemotherapy is considered the best approach in the management of malaria pathogenesis symptomized with hyperparasitemia and oxidative stress because of free radicals’ production; however, a crucial step in the production of DNA is the reversible phosphorylation of dTMP to dTDP, which is catalyzed by Plasmodium falciparum thymidylate kinase. Ethnopharmacologically and scientifically, Mangifera indica is used in the treatment of malaria, thereby necessitating antiplasmodial and antioxidant screening of the plant extract, as well as its in silico profiling to unravel the pharmacological and docking potentials of its bioactive compounds against thymidylate kinase. Methods The collection of the Mangifera indica stem bark, extract preparation, in vivo antiplasmodial assay, in vitro antioxidant assay, retrieval of Plasmodium falciparum thymidylate kinase, and gas chromatography-mass spectrophotometry (GC-MS) were done using standard protocols. The SwissADME tool was used in the prediction of the physicochemical, drug-likeness, and pharmacokinetic properties, whereas molecular docking analysis was done with the MCULE tool. Results The GC-MS profiling revealed mangiferin, d-idopyranoside, lauric acid, fatty acid, isoprene derivatives, etc; these compounds contributed immensely to the plant's antioxidant and antiplasmodial (87.71%) potentials. Also, the compounds (55.7%) successfully docked the active sites of thymidylate kinase; 72.1% and 57.4% revealed high rates of gastrointestinal tract (GIT) absorption and distribution in the interstitial tissues, respectively, whereas 98.4% were not substrates of permeation glycoprotein. However, the % non-inhibition of CYP1A2, CYP2C19, CYP2C9, CYP2D6, and CYP3A4 were 45.9, 98.4, 67.2, 95.1, and 98.4, respectively, while drug-likeness revealed 100% Lipinski's compliance. Conclusion The observed antiplasmodial, antioxidant, and pharmacological properties could be due to the presence of the glucosyl xanthone, idopyranoside, fatty acid, and isoprene derivatives.