Quercetin-3-O-galactoside from Garcinia Kola Heckel stem bark as a potential bioactive inhibitor against histone deacetylase 8 (HDAC8) using in silico study

The stem bark of Garcinia kola Heckel (Clusiaceae) is frequently used as antitumor in Southern Nigeria. The study aimed to evaluate antioxidant, cytotoxic, and inhibitory activities from the extract and fractions of G. kola and assess their potential use as histone deacetylase (HDAC8) inhibitors in cancer therapy. Antioxidant and cytotoxicity assays were performed on the methanol (MeOH) stem bark extract and fractions [n-hexane, dichloromethane (DCM), ethyl acetate (EtOAc)]. Bioactive compounds from the n-hex fraction were suitably prepared and docked using the Ligprep and Glide modules of Schrodinger. The inhibitory concentration (IC50 in µg/mL) values of the free radical scavenging activity using 1,1-diphenyl-2-picryl-hydrazyl (DPPH) was highest in the EtOAc fraction (16.70 ± 4.48) followed by n-hexane fraction (25.30 ± 2.67), and 35.50 ± 1.47 in the MeOH extract, compared to ascorbic acid (12.17 ± 2.36). The MeOH extract, n-hexane, and DCM fractions had lethal concentration (LC50 in µg/mL) values of 207.50 ± 2.50, 5.50 ± 0.50 and 5.00 ± 0.00, respectively, compared to cyclophosphamide, 58.00 ± 12.50. After 96 h, the mean length of 85.75 ± 1.20 mm in the control of Sorghum bicolor radicle seeds was reduced to 41.07 ± 0.97 and 18.53 ± 2.32 mm when treated with 2 and 3 mg/mL of n-hexane fraction, corresponding to 52.10 and 78.39%, inhibitory reductions respectively. Furthermore, the molecular docking results revealed that quercetin-3-O-galactoside demonstrated the strongest affinity for the HDAC8 protein, forming stable interactions within the binding site and establishing three prominent hydrogen bonds with the residues Lys33, His143, and Tyr306. These results suggest that quercetin-3-O-galactoside could be the bioactive inhibitor from the n-hexane fraction of Garcinia kola possessing potential antioxidant, cytotoxic, and inhibitory activities.