Physapubescin, a natural withanolide as a kidney-type glutaminase (KGA) inhibitor

Li Cheng; Can-Rong Wu; Li-Han Zhu; Hua Li; Li-Xia Chen

doi:10.1016/j.bmcl.2017.01.057

Physapubescin, a natural withanolide as a kidney-type glutaminase (KGA) inhibitor

Bioorg Med Chem Lett. 2017 Mar 1;27(5):1243-1246. doi: 10.1016/j.bmcl.2017.01.057. Epub 2017 Jan 21.

Authors

Li Cheng¹, Can-Rong Wu², Li-Han Zhu³, Hua Li⁴, Li-Xia Chen⁵

Affiliations

¹ Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China; School of Traditional Chinese Materia Medica, Wuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
² Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
³ School of Traditional Chinese Materia Medica, Wuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
⁴ Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China; School of Traditional Chinese Materia Medica, Wuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China. Electronic address: [email protected].
⁵ School of Traditional Chinese Materia Medica, Wuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China. Electronic address: [email protected].

PMID: 28174105
DOI: 10.1016/j.bmcl.2017.01.057

Abstract

Kidney-type glutaminase (KGA) is over expressed in many kinds of cancers that converts glutamine to glutamate for supplying energy, and has become an object for targeted cancer therapy. The structure-based virtual ligand screening identified physapubescin, a withanolide purified from Physalis pubescens L., as a possible inhibitor of KGA with low binding energy. Enzyme inhibition experiments and cell-based assays further confirmed its inhibitory effects on KGA activity, suggesting potential applications of physapubescin and its derivatives as KGA inhibitors.

Keywords: Cytotoxicity; Enzyme inhibition; KGA inhibitor; Physapubescin; Structure-based virtual ligand screening.

Publication types

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

MeSH terms

Animals
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology
Biological Assay
Cell Line, Tumor
Enzyme Activation / drug effects
Glutaminase / antagonists & inhibitors*
Humans
Inhibitory Concentration 50
Kidney / enzymology
Ligands
Molecular Docking Simulation
Molecular Structure
Solanaceae / chemistry
Withanolides / chemistry
Withanolides / pharmacology*

Substances

Antineoplastic Agents
Ligands
Withanolides
physapubescin
Glutaminase