Antioxidant Activity, Phytochemical Profiling by UPLC-QTOF-MS, and In Silico Targeting of the RNA-Binding Protein DRBD18 of Trypanosoma brucei by Bioactive Compounds from Tetradenia riparia and Tetracera poggei

Abstract

Oxidative stress plays a key role in the pathogenesis of African trypanosomiasis, and plant-derived antioxidants represent a promising source of dual-action compounds capable of both scavenging reactive oxygen species and interfering with parasite survival. The present study investigates the antioxidant activity and phytochemical composition of two Central African medicinal plants, Tetradenia riparia (Hochst.) Codd and Tetracera poggei (Gilg.) and evaluates the in silico trypanocidal potential of their major constituents against the mRNA-binding protein DRBD18 of Trypanosoma brucei. Aqueous and methanolic extracts were prepared by decoction and percolation. Qualitative phytochemical screening and quantitative spectrophotometry (Folin–Ciocalteu, AlCl3) revealed rich profiles of polyphenols, flavonoids, tannins, anthocyanins, and alkaloids in both species. UPLC-QTOF-MS in negative ESI mode identified eleven compounds in T. riparia, including rosmarinic acid, luteolin, acacetin, and diterpenoid SP-II and thirteen compounds in T. poggei, dominated by galloylated catechin derivatives (epi-gallocatechin 3-O-gallate, catechin 3-O-gallate, (−)-epicatechin-3-(3-O-methyl)- gallate). Antioxidant activity by DPPH and ABTS radical scavenging assays showed that percolated extracts consistently outperformed decocted extracts; T. poggei percolated extract showed the strongest DPPH activity (IC50 = 4.141 ± 0.175 µg/mL). Molecular docking against the RRM1 and RRM2 domains of DRBD18 (AlphaFold model AF-Q57XR9-F1) revealed that diterpenoid SP-II and (−)- epicatechin-3-(3-O-methyl)-gallate displayed the highest binding affinities (RRM1: −7.3 kcal/mol; Ki = 4.424 µM). The strong antioxidant capacity of the identified compounds, particularly galloylated catechins and rosmarinic acid, is mechanistically linked to their structural features that also favor RRM domain binding, highlighting a dual antioxidant–antiparasitic pharmacological profile. These findings provide a rational basis for the further development of plant-derived agents targeting oxidative stress and RNA-binding mechanisms in T. brucei.