Isolation and structural elucidation of biflavonoids from the roots of Garcinia gnetoides (Clusiaceae) as potent anti-HIV agent: insight from molecular docking simulation

Abstract

The main objective of this research is to isolate biflavonoids from the roots of Garcinia gnetoides, having a potential inhibitory effect against HIV-I integrase enzyme. To achieve our objective, we resorted to the phytochemical study of the acetone extract of these roots, from which six pure compounds were isolated. Only two of these compounds (GGB and GGF) were fully characterized and elucidated using spectrometric (HR-ESI mass spectrometry) and spectroscopic methods (1H NMR, 13C NMR, 1H-1H COSY, HMBC, HSQC and ROESY). From that, GGB and GGF were identified as: 6"-O-acetyl-3ʹ-O-methylorientin-[I-(3)-II-(6)]-6"-O-acetyl-3'-O-methylorientin and 6"- (I) – O - acetyl vitexin-[ I- (3) -II - (3') ] - orientin respectively. Their inhibitory activity against HIV-I integrase and their respective cytotoxicity concentration were evaluated. According to the results, GGF (IC50= 3.1 μM) presented a noteworthy inhibitory effect against HIV-I integrase in vitro but was shown cytotoxic (CC50= 5.2 μM) meanwhile, GGB was shown inactive. A pure competitive inhibitor of HIV-I integrase named Chicoric acid was used as control during these evaluations. In order to validate the therapeutic effect of these two biflavonoids, in silico investigations were carried out. The upshot revealed that, GGF and GGB have lower binding scores (-8.92 Kcal/mol and -6.4 Kcal/mol respectively) compared to Chicoric acid (-5.56 Kcal/mol)