A novel terpenoid, coffeacanol B (1), and nine recognized chemicals (2-10) were found in Coffea canephora husks. DP4 probability analysis verified its absolute configuration. Compounds 1, 3, 4, 8, and 10 inhibited alpha-glucosidase with IC50 values ranging from 21.7 to160.3 µM, surpassing the positive control, acarbose. Compound 10, reduced NO generation, and entry 7 showed potent efficacy, comparable to diclofenac. Compound 1 was the most effective against MCF-7 cells (IC50 = 18.69 µM), while compound 4 showed the strongest activity against HepG2 cells (IC50 = 16.14 µM). Compound 8 docked for alpha-glucosidase inhibition, 4J5T:pdb, compounds 7 and 8 anchored to 4WCU:pdb for anti-inflammatory activity, and compound 4 bonded to 1T8I:pdb for anticancer activity. The pose 89/(8) is the most favorable conformation against 4J5T, with ΔG° = -9.79 kcal mol- 1, Ki = 0.067 µM, consistent with its high in vitro activity. Compound 4/pose 885 exposed strong binding to 1T8I, with ΔG° = -7.68 kcal mol- 1, Ki = 2.36 µM. Molecular dynamics (MD) simulations revealed that the complex of compound 4 and the 1T8I enzyme stabilized after 30 ns, with the ligand RMSD remaining below 2 Å and dominant interactions with Ala 499 (90% of the simulation time), confirming a reliable docking pose.
Le et al. (Sun,) studied this question.