Inhibitory Effect of Gedunin Analogue against the Plasmodium falciparum Dihydrofolate Reductase
V. Amarachukwu Arazu
Department of Science Laboratory Technology, University of Nigeria, Nsukka, Nigeria.
Christian Nelson *
Department of Biochemistry, Taraba State University, Nigeria.
Uzoeto O. Henrietta
Department of Therapy and Applied Science, Federal College of Dental Technology and Therapy, Enugu, Nigeria.
Ayodele Akinwonmi
Department of Chemistry, Federal College of Education, Eha Amufu, Nigeria.
A. Solomon Ochepo
Department of Biochemistry, University of Nigeria, Nsukka, Nigeria.
Cosmas Samuel
Department of Biochemistry, University of Nigeria, Nsukka, Nigeria.
*Author to whom correspondence should be addressed.
Abstract
Objective: Plasmodium parasites are the cause of malaria. Malaria victims get infected upon being bitten by female anopheles mosquito; which transmits the parasite to the victim. The P. falciparum and P. vivax are the most active disease-causing agents of all five malaria-causing species of Plasmodium. The anti-folate drugs which were the first class of clinical antimetabolites act by disrupting metabolic pathways in which the one-carbon moiety supplied by the B9 folate vitamins is a major requirement.
Methods: Chemical structures of the anti-folate drugs which served as the experimental control ligands were downloaded from the PubChem database and saved as PDB files while the gedunin modification was achieved using the Marvin-Sketch software.
Results: Molecular visualization of the polar interactions with amino acid residues of the Plasmodium falciparum dihydrofolate-reductase showed that all the control ligands interacted with similar residues contrary to the interaction of the gedunin modified ligand in the same binding pocket.
Conclusion: Results from the molecular docking study showed that gedunin and its C=O of gedunin might be better antimalarial agents; having exhibited the best binding energies with a score of -9.5 and -9.0 Kcal/mol respectively.
Keywords: Plasmodium falciparum, anti-folate drugs, gedunin, molecular docking, dihydrofolate reductase