Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Chemical constituents of Combretum dolichopetalum: Characterization, antitrypanosomal activities and molecular docking studies

Charles O Nnadi¹ , Raphael Onuku¹, Thecla O Ayoka², Ndidiamaka H Okorie³, Ngozi J Nwodo¹

¹Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka, Nigeria; ²Department of Science Laboratory Technology (Biochemistry Unit), Faculty of Physical Science, University of Nigeria, Nsukka 410001, Nigeria; ³Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Enugu State University of Science and Technology, Enugu, Nigeria.

For correspondence:- Charles Nnadi Email: charles.nnadi@unn.edu.ng Tel:+2348064947734

Accepted: 28 March 2022 Published: 30 April 2022

Citation: Nnadi CO, Onuku R, Ayoka TO, Okorie NH, Nwodo NJ. Chemical constituents of Combretum dolichopetalum: Characterization, antitrypanosomal activities and molecular docking studies. Trop J Pharm Res 2022; 21(4):810-808 doi: 10.4314/tjpr.v21i4.17

© 2022 The authors.
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Abstract

Purpose: To evaluate the in vitro activities of a gallic acid ester and two apigenin flavone glucoside constituents of Combretum dolichopetalum against Trypanosoma brucei brucei s427 (Tbs427) and Trypanosoma congolense IL3000 (Tc-IL3000), and their interactions with a lysosomal papain-like cysteine protease (CP) enzyme in silico.

Methods: Anti-trypanosomal activity-guided separation of ethyl acetate fraction using column chromatographic (CC) technique and purification of the CC sub-fractions with semi-preparative HPLC yielded three (1-3) compounds. The structures were characterized based on nuclear magnetic resonance (NMR) spectroscopic analyses and tested for activities against Tbs427 and Tc-IL3000. All the compounds were subjected to molecular docking studies for the inhibition of trypanosomal cathepsin B (TbCatB) CP.

Results: An ester (1), a butyl gallate, and two positional isomeric apigenin flavone glucosides (2, 3) were identified. The compounds 2 (vitexin) and 3 (isovitexin) showed low in vitro IC₅₀ against the tested parasites. However, 2 (IC₅₀, 25 μM) was more potent than 3 (IC₅₀, 68 μM) against Tbs427 while both were equipotent (IC₅₀ = 2, 11.5 μM and 3, 10.8 μM) against Tc-IL3000. Compound 1 (butyl gallate) showed higher activity against Tc-IL3000 (IC₅₀ = 0.80 μM) than to Tbs427 (IC₅₀, 2.72 μM). The molecular docking study showed that all the compounds had minimum binding energies with a higher affinity towards the active pocket of TbCatB compared to the controls and native inhibitor (CA074).

Conclusion: The relatively high in vitro activities and their strong affinity for TbCatB support the need for further optimization of the compounds towards lead identification against animal trypanosomiasis.

Keywords: Cathepsin B, Combretum dolichopetalum, Docking, Flavone, Gallate, Afican trypanosomasis