title: Design, synthesis and docking study of novel tetracyclic oxindole derivatives as α-glucosidase inhibitors.
abstract: A series of novel tetracyclic oxindole derivatives were synthesized via tandem Suzuki coupling-Michael addition reaction catalyzed by palladium. Twenty derivatives were designed and synthesized in 6-8 steps in 8-20% overall yields. Their structures were confirmed by (1)H, (13)C NMR and LC/MS. These compounds were evaluated for α-glucosidase inhibitory activity in vitro. Compounds 7c, 7d, 7e, 7g, 7h, and 7i exhibited IC50 values of 32.3, 12.1, 15.7, 29.0, 16.0, and 4.8 μM, respectively, with potency all higher than that of the control standard acarbose (IC50=115.8 μM). Molecular docking studies revealed the existence of potential hydrogen bonding and hydrophobic interaction between the enzyme and the active compound 7i.
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology (Tianjin University of Science and Technology), Ministry of Education, Tianjin 300457, China; Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China; Sino-French Joint Lab of Food Nutrition/Safety and Medicinal Chemistry, Tianjin University of Science and Technology, Tianjin 300457, China.
authors.forename: Kailin
authors.initials: K
authors.lastname: Han
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology (Tianjin University of Science and Technology), Ministry of Education, Tianjin 300457, China; Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China; Sino-French Joint Lab of Food Nutrition/Safety and Medicinal Chemistry, Tianjin University of Science and Technology, Tianjin 300457, China.
authors.forename: Yashan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology (Tianjin University of Science and Technology), Ministry of Education, Tianjin 300457, China; Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China; Sino-French Joint Lab of Food Nutrition/Safety and Medicinal Chemistry, Tianjin University of Science and Technology, Tianjin 300457, China.
authors.forename: Yazhou
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology (Tianjin University of Science and Technology), Ministry of Education, Tianjin 300457, China; Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China; Sino-French Joint Lab of Food Nutrition/Safety and Medicinal Chemistry, Tianjin University of Science and Technology, Tianjin 300457, China.
authors.forename: Yuou
authors.initials: Y
authors.lastname: Teng
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Meiyan
authors.initials: M
authors.lastname: Wang
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Runling
authors.initials: R
authors.lastname: Wang
authors.affiliation: Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research (TIPR), Tianjin 300193, China.
authors.forename: Weiren
authors.initials: W
authors.lastname: Xu
authors.affiliation: Sphinx Scientific Laboratory, 1250 East State Street, Sycamore, IL 60178, USA.
authors.forename: Qingwei
authors.initials: Q
authors.lastname: Yao
authors.affiliation: Sino-French Joint Lab of Food Nutrition/Safety and Medicinal Chemistry, Tianjin University of Science and Technology, Tianjin 300457, China.
authors.forename: Yongmin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology (Tianjin University of Science and Technology), Ministry of Education, Tianjin 300457, China.
authors.forename: Haijuan
authors.initials: H
authors.lastname: Qin
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology (Tianjin University of Science and Technology), Ministry of Education, Tianjin 300457, China; Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China; Sino-French Joint Lab of Food Nutrition/Safety and Medicinal Chemistry, Tianjin University of Science and Technology, Tianjin 300457, China. Electronic address: sunhua@tust.edu.cn.
authors.forename: Hua
authors.initials: H
authors.lastname: Sun
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology (Tianjin University of Science and Technology), Ministry of Education, Tianjin 300457, China; Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China; Sino-French Joint Lab of Food Nutrition/Safety and Medicinal Chemistry, Tianjin University of Science and Technology, Tianjin 300457, China. Electronic address: yupeng@tust.edu.cn.
authors.forename: Peng
authors.initials: P
authors.lastname: Yu
mesh_terms: D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D065089:Glycoside Hydrolase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D026121:Indole Alkaloids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D000520:alpha-Glucosidases / Q000378:metabolism*
chemical_list: D065089:Glycoside Hydrolase Inhibitors; D026121:Indole Alkaloids; D000520:alpha-Glucosidases
keywords: Docking study; Phenanthridine derivatives; SAR study; Tetracyclic isatins; α-Glucosidase inhibitors