Cytotoxic and α-Glucosidase Inhibitory Xanthones from Garcinia mckeaniana Leaves and Molecular Docking Study.

Abstract

A new racemic xanthone,\xa0garmckeanin A ( 1 ), and eight known analogues 2 -9 \xa0were isolated from the ethyl acetate (EtOAc) extract of the Vietnamese Garcinia mckeaniana leaves. Their structures were determined by MS and NMR spectral analyses and compared with the literature. The EtOAC extract showed good cytotoxicity against cancer cell lines KB, Lu, Hep-G2 and MCF7, with IC 50 \xa0values of 5.40-8.76 µg/mL, and it also possessed α-glucosidase inhibitory activity, with an IC 50 \xa0value of 9.17 µg/mL. Garmckeanin A ( 1 ) exhibited inhibition of all cancer cell lines, with an IC 50 \xa0value of 7.3-0.9 μM. Allanxanthone C ( 5 ) successfully controlled KB growth, with an IC 50 \xa0value of 0.54 μM, higher than that of the positive control, ellipticine (IC 50 1.22 μM). Norathyriol ( 8 ) was a promising α-glucosidase inhibitor, with an IC 50 \xa0value of 0.07 μM, much higher than that of the positive control, acarbose (IC 50 \xa0161.0 μM). The interactions of the potential α-glucosidase inhibitors with the C- and N-terminal domains of human intestinal α-glucosidase were also investigated by molecular docking study. The results indicated that bannaxanthone D ( 2 ), garcinone E ( 4 ), bannaxanthone E ( 6 ), and norathyriol ( 8 ) exhibit higher binding affinity to the C-terminal than to the N-terminal domain through essential residues in the active sites. In particular, compound 8 \xa0could be assumed to be the most potent mixed inhibitor.