PreprintArticleVersion 1Preserved in Portico This version is not peer-reviewed
Virtual Screening of Selected Phytochemicals From Four Antimalarial Plants Predicted Potential Inhibitors of Wild Type and Mutant Forms of Dihydrofolate Reductase-Thymidylate Synthase in Plasmodium sp.
Version 1
: Received: 1 February 2022 / Approved: 8 February 2022 / Online: 8 February 2022 (12:06:36 CET)
How to cite:
Ikegbunam, M.; Ejiofor, I.; Duru, V.; Akachukwu, A.; Oranu, E.; Okoyeh, J.N.; Egieyeh, S. Virtual Screening of Selected Phytochemicals From Four Antimalarial Plants Predicted Potential Inhibitors of Wild Type and Mutant Forms of Dihydrofolate Reductase-Thymidylate Synthase in Plasmodium sp.. Preprints2022, 2022020107. https://doi.org/10.20944/preprints202202.0107.v1
Ikegbunam, M.; Ejiofor, I.; Duru, V.; Akachukwu, A.; Oranu, E.; Okoyeh, J.N.; Egieyeh, S. Virtual Screening of Selected Phytochemicals From Four Antimalarial Plants Predicted Potential Inhibitors of Wild Type and Mutant Forms of Dihydrofolate Reductase-Thymidylate Synthase in Plasmodium sp.. Preprints 2022, 2022020107. https://doi.org/10.20944/preprints202202.0107.v1
Ikegbunam, M.; Ejiofor, I.; Duru, V.; Akachukwu, A.; Oranu, E.; Okoyeh, J.N.; Egieyeh, S. Virtual Screening of Selected Phytochemicals From Four Antimalarial Plants Predicted Potential Inhibitors of Wild Type and Mutant Forms of Dihydrofolate Reductase-Thymidylate Synthase in Plasmodium sp.. Preprints2022, 2022020107. https://doi.org/10.20944/preprints202202.0107.v1
APA Style
Ikegbunam, M., Ejiofor, I., Duru, V., Akachukwu, A., Oranu, E., Okoyeh, J.N., & Egieyeh, S. (2022). Virtual Screening of Selected Phytochemicals From Four Antimalarial Plants Predicted Potential Inhibitors of Wild Type and Mutant Forms of Dihydrofolate Reductase-Thymidylate Synthase in <em>Plasmodium sp</em>.. Preprints. https://doi.org/10.20944/preprints202202.0107.v1
Chicago/Turabian Style
Ikegbunam, M., Jude Nnaemeka Okoyeh and Samuel Egieyeh. 2022 "Virtual Screening of Selected Phytochemicals From Four Antimalarial Plants Predicted Potential Inhibitors of Wild Type and Mutant Forms of Dihydrofolate Reductase-Thymidylate Synthase in <em>Plasmodium sp</em>." Preprints. https://doi.org/10.20944/preprints202202.0107.v1
Abstract
Resistance to Pyrimethamine, an antimalarial medicine has been reported to be due to mutations in Dihydrofolate reductase-thymidylate synthase (DHFR-TS). Phytochemicals, particularly from plants that been used in ethnomedicine, have been reported to have privileged structures that might bind strongly to the mutants of DHFR-TS. The aim of this study is to identify phytochemicals of Acalypha wilkesiana, Cymbopogon citratus, Azadirachta indica, and Morinda lucida with high binding affinities for the Plasmodium falciparum DHFR-TS. The three-dimensional structures of the phytochemicals, wide type and mutant forms of DHTR-TS were obtained from PubChem and Protein Databank (PDB) respectively. They were appropriately prepared and molecular docking simulations was implemented to predict binding affinities of the phytochemicals to the wildtype and mutant forms of DHTR-TS. Druglikeness assessment was implemented to triage the top binding phytochemicals and molecular dynamics simulations was done to establish the stability of the interaction of the top-ranked phytochemical with one of the mutants of DHFR-TS. Nineteen phytochemicals showed higher binding affinities to both the wild type and mutant forms DHFR-TS than Pyrimethamine. Molecular dynamics revealed that the receptor-ligand binding of luteolin, the top-ranked, drug like phytochemicals, to the quadruple mutant was stable.
Medicine and Pharmacology, Pharmacology and Toxicology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
