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.
Li Cheng  1 ,  Can-Rong Wu  2 ,  Li-Han Zhu  3 ,  Hua Li  4 ,  Li-Xia Chen  5
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.