Computational study of phytochemicals from Khaya grandifoliola (WELW) as potential inhibitors of the Plasmodium falciparum transketolase and putative antimalarial agents.

Abstract

The tropical and subtropical region has been challenged with Malaria; a life-threatening disease caused by Plasmodium falciparum. The rise of anti-malarial drug resistance, especially drug resistant Plasmodium falciparum strains has led to the urgent need for novel antimalarial drugs. This study focuses on using computational techniques to investigate and profile phytochemicals found in K. grandifoliola, a plant known for its medicinal use in Africa for treating malaria in particular, as potential inhibitors of the Plasmodium falciparum transketolase enzyme and putative antimalarial agents. Computational techniques, including molecular docking and molecular dynamics simulations, were employed to assess the binding affinity, stability, and interactions of the identified phytochemicals with the target protein. The findings revealed that three phytochemicals, Khivorin (AKT-6), 7-deacetylkhivorin (AKT-18), and 1-deacetylkhivorin (AKT-22), exhibited favorable pharmacokinetic properties, drug-likeness, and strong binding affinity for the P. falciparum transketolase. Molecular dynamics simulations confirmed the stability of the protein-ligand complexes, further supporting the potential of these compounds as inhibitors. The identified phytochemicals that demonstrated significant binding potential and stability upon forming complex with transketolase, having optimum pharmacokinetics, suggests their potential as lead compounds for future drug discovery efforts.

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