Bioactive Compounds From Coffea canephora Husks: Alpha Glucosidase Inhibition, Anti‐Inflammatory Potential, Cytotoxicity, and In Silico Docking

ABSTRACT 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 IC 50 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 (IC 50 = 18.69 µM), while compound 4 showed the strongest activity against HepG2 cells (IC 50 = 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 Δ G ° = −9.79 kcal mol − 1 , K i = 0.067 µM, consistent with its high in vitro activity. Compound 4/ pose 885 exposed strong binding to 1T8I, with Δ G ° = −7.68 kcal mol − 1 , K i = 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.