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

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.