Protein tyrosine phosphatase 1B (PTP1B) inhibitorsfrom the deep-sea fungus Penicillium chrysogenum SCSIO 07007

Wenrong Han; Jia Cai; Weimao Zhong; Guangming Xu; Fazuo Wang; Xinpeng Tian; Xiaojiang Zhou; Qingchao Liu; Yonghong Liu; Junfeng Wang

doi:10.1016/j.bioorg.2020.103646

Protein tyrosine phosphatase 1B (PTP1B) inhibitorsfrom the deep-sea fungus Penicillium chrysogenum SCSIO 07007

Bioorg Chem. 2020 Mar:96:103646. doi: 10.1016/j.bioorg.2020.103646. Epub 2020 Feb 1.

Authors

Wenrong Han¹, Jia Cai², Weimao Zhong³, Guangming Xu⁴, Fazuo Wang³, Xinpeng Tian³, Xiaojiang Zhou⁵, Qingchao Liu⁶, Yonghong Liu³, Junfeng Wang⁷

Affiliations

¹ CAS Key Laboratory of Tropical Marine Bio-resources and Ecology/Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China; College of Chemical Engineering, Department of Pharmaceutical Engineering, Northwest University, Xi'an 710069, China.
² CAS Key Laboratory of Tropical Marine Bio-resources and Ecology/Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China; College of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China.
³ CAS Key Laboratory of Tropical Marine Bio-resources and Ecology/Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China.
⁴ College of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China.
⁵ College of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China. Electronic address: gale9888@163.com.
⁶ College of Chemical Engineering, Department of Pharmaceutical Engineering, Northwest University, Xi'an 710069, China. Electronic address: liuqc21@nwu.edu.cn.
⁷ CAS Key Laboratory of Tropical Marine Bio-resources and Ecology/Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China. Electronic address: wangjunfeng@scsio.ac.cn.

PMID: 32036160
DOI: 10.1016/j.bioorg.2020.103646

Abstract

Three new compounds, including two new 3,4,6-trisubstituted α-pyrone derivatives, chrysopyrones A and B (1 and 2), and one new indolyl diketopiperazine derivative, penilline C (3), along with twelve known compounds (4-15), were isolated and identified from the fungus Penicillium chrysogenum SCSIO 07007, separated from deep-sea hydrothermal vent environment sample collected from the Western Atlantic. Their structures and absolute configurations were determined by extensive spectroscopic analysis and electronic circular dichroism (ECD) calculations. All of the isolated compounds (1-15) were evaluated for their cytotoxic, antibacterial activities and enzyme inhibitory activities against acetylcholinesterase (AChE), α-glycosidase, and protein tyrosine phosphatase 1B (PTP1B). Among them, new compounds chrysopyrones A and B (1 and 2) displayed obvious inhibitory activities against PTP1B with IC₅₀ values of 9.32 and 27.8 μg/mL, respectively. Furthermore, molecular docking was performed to investigate the inside perspective of the action in PTP1B enzyme.

Keywords: Indolyl diketopiperazine; Penicillium chrysogenum; Protein tyrosine phosphatase 1B inhibition; α-pyrone.

Publication types

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

MeSH terms

Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / isolation & purification
Anti-Bacterial Agents / pharmacology
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / isolation & purification
Enzyme Inhibitors / pharmacology*
Humans
Molecular Docking Simulation
Penicillium chrysogenum / chemistry*
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
Pyrones / chemistry
Pyrones / isolation & purification
Pyrones / pharmacology

Substances

Anti-Bacterial Agents
Enzyme Inhibitors
Pyrones
PTPN1 protein, human
Protein Tyrosine Phosphatase, Non-Receptor Type 1