Synthesis, α-glucosidase inhibitory and molecular docking studies of prenylated and geranylated flavones, isoflavones and chalcones

Hua Sun; Yashan Li; Xiaoting Zhang; Yanan Lei; Weina Ding; Xue Zhao; Haomeng Wang; Xiaotong Song; Qingwei Yao; Yongmin Zhang; Ying Ma; Runling Wang; Tao Zhu; Peng Yu

doi:10.1016/j.bmcl.2015.08.059

Synthesis, α-glucosidase inhibitory and molecular docking studies of prenylated and geranylated flavones, isoflavones and chalcones

Bioorg Med Chem Lett. 2015 Oct 15;25(20):4567-71. doi: 10.1016/j.bmcl.2015.08.059. Epub 2015 Aug 21.

Authors

Hua Sun¹, Yashan Li¹, Xiaoting Zhang¹, Yanan Lei¹, Weina Ding¹, Xue Zhao¹, Haomeng Wang¹, Xiaotong Song¹, Qingwei Yao², Yongmin Zhang³, Ying Ma⁴, Runling Wang⁴, Tao Zhu⁵, Peng Yu⁶

Affiliations

¹ Key Laboratory of Industrial Fermentation Microbiology (Tianjin University of Science and Technology), Ministry of Education, Tianjin 300457, China; Tianjin Key Laboratory of Industry Microbiology, and Sino-French Joint Lab of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China.
² 382 Longvalley Lane, DeKalb, USA.
³ Tianjin Key Laboratory of Industry Microbiology, and Sino-French Joint Lab of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China; Université Pierre et Marie Curie-Paris 6, Institut Parisien de Chimie Moléculaire UMR CNRS 8232, 4 place Jussieu, 75005 Paris, France.
⁴ School of Pharmacy, Tianjin Medical University, Tianjin 300070, China.
⁵ Key Laboratory of Industrial Fermentation Microbiology (Tianjin University of Science and Technology), Ministry of Education, Tianjin 300457, China; Tianjin Key Laboratory of Industry Microbiology, and Sino-French Joint Lab of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China. Electronic address: tao.zhu@cansinotech.com.
⁶ Key Laboratory of Industrial Fermentation Microbiology (Tianjin University of Science and Technology), Ministry of Education, Tianjin 300457, China; Tianjin Key Laboratory of Industry Microbiology, and Sino-French Joint Lab of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China. Electronic address: yupeng@tust.edu.cn.

PMID: 26351039
DOI: 10.1016/j.bmcl.2015.08.059

Abstract

Three series of prenylated and/or geranylated flavonoids were synthesized and evaluated for their α-glucosidase inhibitory activity. The 3',5'-digeranylated chalcone (16) was identified as a new α-glucosidase inhibitor whose activity (IC50=0.90 μM) was 50-fold more than that of acarbose (IC50=51.32 μM). Molecular docking studies revealed the existence of strong hydrophobic interaction and H-bonding between compound 16 and α-glucosidase's active site. The inhibitory mode analysis showed that 16 exhibited a competitive inhibitory mode.

Keywords: Docking study; Flavonoid; Geranyl; Prenyl; α-Glucosidase inhibitors.

Publication types

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

MeSH terms

Chalcones / chemical synthesis
Chalcones / chemistry
Chalcones / pharmacology*
Dose-Response Relationship, Drug
Flavones / chemical synthesis
Flavones / chemistry
Flavones / pharmacology*
Glycoside Hydrolase Inhibitors / chemical synthesis
Glycoside Hydrolase Inhibitors / chemistry
Glycoside Hydrolase Inhibitors / pharmacology*
Humans
Isoflavones / chemical synthesis
Isoflavones / chemistry
Isoflavones / pharmacology*
Molecular Docking Simulation*
Molecular Structure
Structure-Activity Relationship
alpha-Glucosidases / metabolism*

Substances

Chalcones
Flavones
Glycoside Hydrolase Inhibitors
Isoflavones
alpha-Glucosidases