Anti-diabetic xanthones from the bark of Garcinia xanthochymus

Chi N Nguyen; Binh T D Trinh; Toan B Tran; Le-Thu T Nguyen; Anna K Jäger; Lien-Hoa D Nguyen

doi:10.1016/j.bmcl.2017.06.021

Anti-diabetic xanthones from the bark of Garcinia xanthochymus

Bioorg Med Chem Lett. 2017 Aug 1;27(15):3301-3304. doi: 10.1016/j.bmcl.2017.06.021. Epub 2017 Jun 8.

Authors

Chi N Nguyen¹, Binh T D Trinh², Toan B Tran¹, Le-Thu T Nguyen¹, Anna K Jäger³, Lien-Hoa D Nguyen⁴

Affiliations

¹ Natural Product and Medicinal Chemistry Lab, Faculty of Chemistry, VNUHCM-University of Science, 227 Nguyen Van Cu, Ho Chi Minh City, Viet Nam.
² Natural Product and Medicinal Chemistry Lab, Faculty of Chemistry, VNUHCM-University of Science, 227 Nguyen Van Cu, Ho Chi Minh City, Viet Nam; Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
³ Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
⁴ Natural Product and Medicinal Chemistry Lab, Faculty of Chemistry, VNUHCM-University of Science, 227 Nguyen Van Cu, Ho Chi Minh City, Viet Nam. Electronic address: nguyendieulienhoa@gmail.com.

PMID: 28624142
DOI: 10.1016/j.bmcl.2017.06.021

Abstract

An ethyl acetate extract the bark of Garcinia xanthochymus exhibited strong inhibition towards α-glucosidase and PTP1B with IC₅₀ values of 0.3±0.1μg/mL and 2.3±0.4μg/mL, respectively. Chemical constituents of the extract were therefore examined, and two new compounds, xanthochymusxanthones A (1) and B (2), along with ten known xanthones (3-12), were isolated. Their structures were determined using spectroscopic methods, mainly 1D and 2D NMR. Inhibitory activity of the isolated compounds was then tested, and subelliptenone F (12) showed significant effect towards α-glucosidase with IC₅₀ value of 4.1±0.3μM (compared with acarbose, IC₅₀=900.0±3.0μM) whilst xanthochymusxanthone B (2) exhibited remarkable activity towards PTP1B with IC₅₀ value of 8.0±0.6μM (compared with RK682, IC₅₀=4.4±0.3μM).

Keywords: Anti-diabetic activity; Garcinia xanthochymus; PTP1B inhibition; Structure determination; Xanthones; α-Glucosidase.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Diabetes Mellitus / drug therapy
Diabetes Mellitus / metabolism
Garcinia / chemistry*
Glycoside Hydrolase Inhibitors / chemistry*
Glycoside Hydrolase Inhibitors / isolation & purification
Glycoside Hydrolase Inhibitors / pharmacology*
Humans
Hypoglycemic Agents / chemistry
Hypoglycemic Agents / isolation & purification
Hypoglycemic Agents / pharmacology
Models, Molecular
Plant Bark / chemistry
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
Xanthones / chemistry*
Xanthones / isolation & purification
Xanthones / pharmacology*
alpha-Glucosidases / metabolism

Substances

Glycoside Hydrolase Inhibitors
Hypoglycemic Agents
Xanthones
PTPN1 protein, human
Protein Tyrosine Phosphatase, Non-Receptor Type 1
alpha-Glucosidases