In silico Anti-malaria Activity of Quinolone Compounds against Plasmodium falciparum Dihydrofolate Reductase (pfDHFR)

Main Article Content

Toheeb A. Balogun
Damilola A. Omoboyowa
Oluwatosin A. Saibu

Abstract

Chemotherapy remains the kernel of malaria control and the available antimalarial drugs are not only expensive but also parade heterogeneous levels of toxicity and may invoke poor compliance in patients. The present study focuses on the screening of quinolone compounds against Plasmodium falciparum dihydrofolate reductase (pfDHFR) for anti-malarial potential using Glide (Schrodinger maestro 2017-1). Computational tool using Glide was employed to investigate the therapeutic relevance of six (6) quinolone derivatives retrieved from PUBCHEM    via molecular docking against pfDHFR retrieved from protein data base. The results showed that, Lascufloxacin and moxifloxacin bind with higher affinity and lower free energy with catalytic domain of pfDHFR with glide score of -6.597 and -5.653 respectively compared to standard ligand (quinine) with glide score of -3.728. Lascufloxacin interacted with amino acid residue of the catalytic domain (SER 511, ARG 510, GLU 382) as evaluated by energy decomposition per residue lascufloxacin-pfDHFRcomplex. The results from this investigation, thus proposed quinolone derivatives as hit lead drug candidates which may be consider as potential inhibitor of pfDHFR.

Keywords:
Quinolone, dihydrofolatereductase, molecular docking, lascufloxacine, Malaria

Article Details

How to Cite
Balogun, T. A., Omoboyowa, D. A., & Saibu, O. A. (2020). In silico Anti-malaria Activity of Quinolone Compounds against Plasmodium falciparum Dihydrofolate Reductase (pfDHFR). International Journal of Biochemistry Research & Review, 29(8), 10-17. https://doi.org/10.9734/ijbcrr/2020/v29i830208
Section
Original Research Article

References

Omoboyowa DA, Nwodo F, Joshua PE. Effects of Combined Treatment of Tithoniadiversifolia and Chloroquine on Selected Organs of Chloroquine Resistant Plasmodium Infected Mice. Asian Journal of Biological Sciences. 2018;11:58-72.

David TI, Niyi SA, Olaposi IO, Damilohun SM, Oluwafemi Gabriel EE, et al. Molecular docking analysis of phyto-constituents from Cannabis sativa with pfDHFR. Bioinformation 2018;14(9):574-579.

Chan J, Talisuna AO, Erhart A, Yeka A, Tibenderana JK, Baliraine FN, et al. Quinine, an old anti-malarial drug in a modern world: role in the treatment of malaria. Malar J. 2011;10:144.

Bunnag D, Karbwang J, Na-Bangchang K, Thanavibul A, Chittamas S, Harinasuta T. Quinine-tetracycline for multidrug resistant falciparum malaria. Southeast Asian J Trop Med Public Health. 1996;27:15–8.

Singh IV, Mishra S. Molecular Docking Analysis of Pyrimethamine Derivatives with Plasmodium falciparum Dihydrofolate Reductase. Bioinformation. 2018;14(5): 232-235.

Shi PW, LiliCK, WangJieZ J. Co (III)-Catalyzed Enaminone-Directed C-H Amidation for Quinolone Synthesis. Organic Letters. 2017;19:2418–2421.

Beteck RM, Smit FJ, Haynes RK, N’Da, DD. Recent progress in the development ofanti-malarial quinolones. Malaria Journal, 2014;13:339

Elekofehinti OO. Molecular docking studies on Borapetol with Target. J of Pharma And Chem. Res. 2015;149-155

Meng XY, Zhang HX, Mezei M, Cui M. Molecular docking: A powerful approach for structure-based drug discovery. Curr. Comput. Aided Drug Des. 2011;7:146-157

Foloppe N, Hubbard R. Towards predictive ligand design with free energy based computational methods? Curr. Med. Chem. 2006;13: 3583-3608.

Jain AN, Scoring functions for protein–ligand docking. Curr. Protein Pept. Sci. 2006;7:407-420.

Kalirajan R, Pandiselvi M, Sankar S, Gowramma B. Molecular Docking Studies and Insilico ADMET Screening of Some Novel Chalcone Substituted 9-Anilinoacridines as Topoisomerase II Inhibitors. SF J Pharm Anal Chem. 2018;1(1):1004.