Format

Send to

Choose Destination
Bioorg Chem. 2017 Dec;75:139-148. doi: 10.1016/j.bioorg.2017.09.001. Epub 2017 Sep 6.

Polycyclic phloroglucinols as PTP1B inhibitors from Hypericum longistylum: Structures, PTP1B inhibitory activities, and interactions with PTP1B.

Author information

1
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, People's Republic of China.
2
College of Chemistry and Environmental Sciences, Laboratory of Xinjiang Native Medicinal and Edible Plant Resources Chemistry, Kashgar University, Kashgar 844000, People's Republic of China.
3
School of Medicine, Nankai University, Tianjin 300071, People's Republic of China.
4
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, People's Republic of China. Electronic address: xujing611@nankai.edu.cn.
5
Department of Biosystems and Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea.
6
Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
7
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, People's Republic of China. Electronic address: victgyq@nankai.edu.cn.

Abstract

Protein tyrosine phosphatase 1B (PTP1B) has been regarded asa target for the research and development of new drugs to treat type II diabetes and PTP1B inhibitors are potential lead compounds for this type of new drugs. A phytochemical investigation to obtain new PTP1B inhibitors resulted in the isolation of four new phloroglucinols, longistyliones A-D (1-4) from the aerial parts of Hypericum longistylum. The structures of 1-4 were elucidated on the basis of extensive 1D and 2D NMR spectroscopic data analysis, and the absolute configurations of these compounds were established by comparing their experimental electronic circular dichroism (ECD) spectra with those calculated by the time-dependent density functional theory method. Compounds 1-4 possess a rare polycyclic phloroglucinol skeleton. The following biological evaluation revealed that all of the compounds showed PTP1B inhibitory effects. The further molecular docking studies indicated the strong interactions between these bioactive compounds with the PTP1B protein, which revealed the possible mechanism of PTP1B inhibition of bioactive compounds. All of the results implied that these compounds are potentially useful for the treatment of type II diabetes.

KEYWORDS:

ECD; Hypericum longistylum; Molecular docking; PTP1B inhibitors; Polycyclic phloroglucinol

PMID:
28946049
DOI:
10.1016/j.bioorg.2017.09.001
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center