In Silico Studies of Bioactive Compounds Selected from Four African Plants with Inhibitory Activity Against Plasmodium falciparum Dihydrofolate Reductase-Thymidylate Synthase (pfDHFR-TS) | ||
| Journal of Advanced Pharmacy Research | ||
| Article 2, Volume 6, Issue 3, July 2022, Pages 107-122 PDF (780.31 K) | ||
| Document Type: Research Article | ||
| DOI: 10.21608/aprh.2022.139794.1175 | ||
| Authors | ||
| Ishola Akinwumi* 1; Ayodele Faleti1; Adefolarin Owojuyigbe1; Faridat Raji2; Michael Alaka3 | ||
| 1Department of Chemistry, School of Physical Sciences, Federal University of Technology, Akure, Ondo State, Nigeria, P.M.B.704 | ||
| 2Department of Biology, School of Life Sciences, Federal University of Technology, Akure, Ondo State, Nigeria, P.M.B.704 | ||
| 3Department of Integrated Science, Lagos State University of Education Otto/Ijanikan, Lagos State, Nigeria, P.M.B.007 | ||
| Abstract | ||
| Objective: This present study aims to assess in silico inhibitory potentials of bioactive compounds present in Vernonia amygdalina (Bitter leaf), Cymbopogon citratus (Lemongrass), Azadirachta indica (Neem leaf), and Carica papaya (Pawpaw leaf) against Plasmodium falciparum Dihydrofolate reductase-thymidylate synthase (pfDHFR-TS) via binding at their active sites. Methods: In silico methods were used in this study. Twenty (20) bioactive compounds were selected from Vernonia amygdalina, Cymbopogon citratus, Azadirachta indica, and Carica papaya. Artemether and Lumefantrine were used as the control drugs. The PubChem identification number (PID), the 3D structure in structure data format (SDF), and the canonical SMILES of the bioactive compounds and the control drugs were obtained using the PubChem online server. The crystal structure of pfDHFR-TS was retrieved from the protein data bank. Drug-likeness of the selected bioactive compounds was assessed using the SwissADME online server. The successful compounds were docked into the protein's active site using AutoDock Vina docking software. The docked complexes were analyzed using proteins plus and protein-ligand interaction profiler web server. The bioactivity of the ligands was determined using the Molinspiration online server. ADMETlab online tool was used to determine the ligands' absorption, distribution, metabolism, excretion, and toxicity (ADMET) characteristics.Results: The drug-likeness screening indicated that eleven (11) out of the twenty bioactive compounds violated two or more of the five rules (Lipinski's, Ghose's, Veber's, Egan's, and Muegge's rules). The control drug Artemether didn't violate any rule, while Lumefantrine violated four out of the five rules. The molecular docking revealed that Nimbolide, Vernomygdin, Luteolin, and Emetine from Azadirachta indica (Neem leaf), Vernonia amygdalina (Bitter leaf), and Carica papaya (Pawpaw leaf) have binding energies of -10.1 kcal/mol, -9.2 kcal/mol, -8.6 kcal/mol, and -9.2 kcal/mol respectively, which are better than the binding energies of Artemether and Lumefantrine (-8.2 kcal/mol, and -7.6 kcal/mol). Thus, these bioactive compounds' binding energies indicate the binding affinity with pfDHFR-TS protein, suggesting that the bioactive compounds may possess a biological activity against malarial. The best four ligands, Nimbolide, Vernomygdin, Luteolin, and Emetine, also showed excellent ADMET properties. Conclusion: Conclusively, the in silico analysis proposes that Nimbolide, Vernomygdin, Luteolin, and Emetine from Azadirachta indica (Neem leaf), Vernonia amygdalina (Bitter leaf), and Carica papaya (Pawpaw leaf) prove to be probable antimalarial drugs, and show better docking with the target protein compared to Artemether and Lumefantrine. To validate this study, an in-vitro and in vivo study is recommended to further this study for validation of the hit compounds, as in silico methods only predict the activity of these bioactive compounds. | ||
| Keywords | ||
| Bioactive compounds; ADMET; Plasmodium falciparum; In silico | ||
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