Synthesis of tetracyclic oxindoles and evaluation of their α-glucosidase inhibitory and glucose consumption-promoting activity

Lei Hao; Yujiao Ma; Lianbo Zhao; Yinan Zhang; Xinying Zhang; Ying Ma; Robert H Dodd; Hua Sun; Peng Yu

doi:10.1016/j.bmcl.2020.127264

Synthesis of tetracyclic oxindoles and evaluation of their α-glucosidase inhibitory and glucose consumption-promoting activity

Bioorg Med Chem Lett. 2020 Jul 15;30(14):127264. doi: 10.1016/j.bmcl.2020.127264. Epub 2020 May 15.

Authors

Lei Hao¹, Yujiao Ma¹, Lianbo Zhao¹, Yinan Zhang¹, Xinying Zhang¹, Ying Ma², Robert H Dodd³, Hua Sun⁴, Peng Yu⁵

Affiliations

¹ China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China.
² School of Pharmacy, Tianjin Medical University, Tianjin 300070, China.
³ China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China; Centre de recherche de Gif-sur-Yvette, Institut de Chimie des Substances Naturelles, UPR 2301, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France.
⁴ China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China. Electronic address: [email protected].
⁵ China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China. Electronic address: [email protected].

PMID: 32527562
DOI: 10.1016/j.bmcl.2020.127264

Abstract

A series of tetracyclic oxindole derivatives was synthesized by asymmetric 1, 3-dipole reaction in 2-4 steps in 57-86% overall yields. These compounds were evaluated for α-glucosidase inhibitory and glucose consumption-promoting activity in vitro. Compound 4l competitively and reversibly inhibited α-glucosidase (IC₅₀ = 3.64 μM) with activity 14-fold higher than that of acarbose. Docking analysis substantiated these findings. In addition, compound 4l exhibited significant glucose consumption promoting activity at 1 μM.

Keywords: Docking analysis; Glucose consumption; Inhibitory mechanism; Tetracyclic oxindole; α-Glucosidase inhibitor.

Publication types

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

MeSH terms

Dose-Response Relationship, Drug
Glucose / metabolism*
Glycoside Hydrolase Inhibitors / chemical synthesis
Glycoside Hydrolase Inhibitors / chemistry
Glycoside Hydrolase Inhibitors / pharmacology*
Hep G2 Cells
Humans
Molecular Docking Simulation
Molecular Structure
Oxindoles / chemical synthesis
Oxindoles / chemistry
Oxindoles / pharmacology*
Structure-Activity Relationship
alpha-Glucosidases / metabolism*

Substances

Glycoside Hydrolase Inhibitors
Oxindoles
alpha-Glucosidases
Glucose