Cytotoxicity, Protein Kinase Inhibitory Activity, and Docking Studies of Secondary Metabolites Isolated from Brownea grandiceps Jacq

Objective: The objective was to study the cytotoxicity, kinase inhibitory activity, and docking of the isolated metabolites. Materials and Methods: Ultraviolet, nuclear magnetic resonance, and mass spectroscopy were used for the identification and confirmation of the active metabolites. Ethyl acetate extract of B. grandiceps was chromatographed. Cytotoxicity (3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide), protein kinase (PK) inhibitory assays, and molecular operating environment (using Molecular Operating Environment [MOE], 2016.08) were performed. Results: Catechin (1), quercitrin (2), trans‑taxifolin‑ 3‑O‑α‑L‑rhamnopyranoside (3), 13R‑hydroxy‑9Z, 11E‑octadecadienoic acid (4), and 13R‑hydroxy‑9Z, 11E‑, 15Z‑octadecatrienoic acid (5) were isolated and identified. Quercitrin (2) exhibited the highest cytotoxicity against MCF‑7 (inhibitory concentration for 50% [IC50]: 4.24 µM) and moderate cytotoxicity against HepG2 cell (IC50: 29.58 µM). Others showed moderate cytotoxicity; compounds 1–3 were tested against Aurora B, CDK4/cyclin D1, COT, IGF1‑R, and FAK PKs, where quercitrin showed the highest inhibitory activity against Aurora B and CDK4/Cyclin D1 (IC50: 4.78 and 3.22 µM). Docking of quercitrin against CDK4/Cyclin D1 confirmed its cytotoxic profile. Conclusion: The metabolites were first isolated from B. grandiceps. The mechanism of action against kinases enzyme was established and confirmed by docking studies of quercitrin at CDK4/Cyclin D1 using MOE program.