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

• Published in: Chemistry & biodiversity 2021-11, Vol.18 (11), p.e2100396-n/a
• Main Authors: Thi Thu, Ha Nguyen, Minh, Quan Pham, Van, Cuong Pham, Van, Tuyen Nguyen, Van, Kiem Phan, Thanh, Tra Nguyen, Le Thi Tu, Anh, Litaudon, Marc, The, Son Ninh
• Format: Article
• Language: English
• Subjects: Acarbose; Acetic acid; alpha-Glucosidases - metabolism; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - isolation & purification; Antineoplastic Agents, Phytogenic - pharmacology; Cancer; Cell Proliferation - drug effects; Chemical Sciences; Cytotoxicity; Domains; Drug Screening Assays, Antitumor; Ethyl acetate; Garcinia; Garcinia - chemistry; Garcinia mckeaniana; Glucosidase; Glycoside Hydrolase Inhibitors - chemistry; Glycoside Hydrolase Inhibitors - isolation & purification; Glycoside Hydrolase Inhibitors - pharmacology; Humans; Inhibitors; Molecular docking; Molecular Docking Simulation; Molecular Structure; NMR; Nuclear magnetic resonance; Organic chemistry; Toxicity; Tumor cell lines; Tumor Cells, Cultured; xanthone; Xanthones - chemistry; Xanthones - isolation & purification; Xanthones - pharmacology; α-glucosidase inhibition
• ISSN: 1612-1872; 1612-1880
• DOI: 10.1002/cbdv.202100396

A new racemic xanthone, garmckeanin A (1), and eight known analogs 2–9 were isolated from the ethyl acetate (AcOEt) extract of the Vietnamese Garcinia mckeaniana leaves. Their structures were determined by MS and NMR spectral analyses and compared with the literature. The AcOEt extract showed good cytotoxicity against cancer cell lines KB, Lu, Hep‐G2 and MCF7, with IC50 values of 5.40–8.76 μg/mL, and it also possessed α‐glucosidase inhibitory activity, with an IC50 value of 9.17 μg/mL. Garmckeanin A (1) exhibited inhibition of all cancer cell lines, with an IC50 value of 7.3–0.9 μM. Allanxanthone C (5) successfully controlled KB growth, with an IC50 value of 0.54 μM, higher than that of the positive control, ellipticine (IC50 1.22 μM). Norathyriol (8) was a promising α‐glucosidase inhibitor, with an IC50 value of 0.07 μM, much higher than that of the positive control, acarbose (IC50 161.0 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 could be assumed to be the most potent mixed inhibitor.