Title: Comparative in-silico parmacokinetics and molecular docking study on gedunin isolated from Azadirachta indica, its modified derivatives and selected antifolate drugs as potential dihydrofolate reductase inhibitors of Plasmodium falciparum

Authors: Samuel Cosmas; Olanrewaju Ayodeji Durojaye; Parker Elijah Joshua; Joyce Oloaigbe Ogidigo; Collins Audu Difa; Justus Nmaduka Nwachukwu

Addresses: Department of Biochemistry, University of Nigeria, Nsukka, Nigeria ' Department of Biochemistry, University of Nigeria, Nsukka, Nigeria ' Department of Biochemistry, University of Nigeria, Nsukka, Nigeria ' Department of Biochemistry, University of Nigeria, Nsukka, Nigeria ' Department of Biochemistry, University of Nigeria, Nsukka, Nigeria ' Department of Biochemistry, University of Nigeria, Nsukka, Nigeria

Abstract: Introduction: Malaria is one of the most common diseases that threaten many of the subtropical and tropical regions. Countries where the risk of transmission of malaria is at the high rate are over a hundred currently and these counties are being visited by over 125, 000, 000 international travelers on yearly basis. Materials and Methods: Chemical structures of ligands were drawn with the MarvinSketch software and converted into SMILES strings for the calculation of pharmacokinetic parameters. Results: The predicted binding energies between the three selected antifolate drugs, gedunin, its derivatives (C=O, C2H5, C3H6O2, C4H8O2, CONH2, NH2, OCH3, OH) and the Plasmodium falciparium DHFR enzyme were -8.0, -7.5, -8.0, -9.5, -9.0, -8.4, -8.9, -8.2, -8.9, -8.7, -8.3, -8.4 Kcal/mol respectively. Conclusion: The results from the experiment showed that gedunin and its modified derivatives might be better antimalarial agents than the antifolate drugs as revealed by the predicted binding energies between the target enzyme and the ligands.

Keywords: Plasmodium; Azadirachta indica; antifolate drugs; parasite; dihydrofolate reductase.

DOI: 10.1504/IJCBDD.2020.107888

International Journal of Computational Biology and Drug Design, 2020 Vol.13 No.3, pp.237 - 254

Received: 15 Nov 2018
Accepted: 13 Apr 2019

Published online: 23 Jun 2020 *

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