In-vitro Antitrypanosomal Activities of the stem bark of Entadrophragma angolense (Meliaceae)

In this study, we investigated the potential antitrypanosomal properties of E. angolense and its possible development as a therapeutic intervention for treating African trypanosomiasis or Sleeping Sickness. In- vitro effects of crude extracts and fractions of stem bark of E. angolense were tested against Trypanosoma brucei using Alamar blue assay. Additionally, the crude extract’s antioxidant (FRAP and DPPH) and cytotoxicity activities were also determined. The phytochemical profiling of the crude extract was determined using LC-ESI-QTOF-MS to identify major bioactive compounds present. E. angolense crude extract and fractions (hexane, chloroform and ethyl acetate) exhibited potential anti-trypanosomal activities with IC₅₀ values of 17.55, 6.8, 6.1 and 22.92 μg/mL respectively. Moreover, the crude extracts were non- toxic against HepG2 and PNT2 cells, with CC₅₀ values of 235.4±0.30 and 548.3±0.09 μg/mL respectively. Antioxidant potential was observed in the crude extracts of E. angolense. LC-MS analysis revealed the presence of 32 bioactive compounds. Furthermore, the bioactive compounds identified were subjected to molecular docking studies to identify novel compounds against Trypanosoma brucei’s UDP-Galactose 4`- Epimerase (TbGalE). Seven (7) potential leads were identified after molecular docking with binding energies -11.4, -11.2, -10.3, -10.2, -10.1, -9.9, -9.3 and -9.1 kcal/mol respectively. Molecular Dynamics simulation and Molecular Mechanics-Poisson Boltzmann Surface Area calculation were performed to elucidate the stability and the binding free energy of the potential leads’ complexes. These compounds will further be investigated experimentally to determine their potential efficacy and could serve as candidates for the design of novel anti-trypanosomal therapeutics.

 

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Publication History

Article published online:
16 November 2023