title: Synthesis and anti-cancer activity evaluation of 5-(2-carboxyethenyl)-isatin derivatives.
abstract: A series of novel di- or trisubstituted isatin derivatives were designed and synthesized in 5-6 steps in 25-45% overall yields. Their structures were confirmed by 1H NMR and 13C NMR as well as LC-MS. The anticancer activity of the fourty-three new isatin derivatives against human T lymphocyte cells Jurkat was evaluated by MTT assay in vitro. SAR study suggested that the combination of 1-benzyl and 5-[trans-2-(methoxycarbonyl)ethen-1-yl] substitution greatly enhanced their cytotoxic activity. Among them, compound 2h was shown to have a significant cytotoxic activity with an IC50 value of 0.03 μM, more than 330-fold higher than that of it's mother molecule isatin. Investigation of the cell morphology changes and annexin-V/PI staining study demonstrated that compound 2h inhibited the proliferation of Jurkat cells by inducing apoptosis. Since compound 2h induced the dissipation of mitochondrial membrane potential and the activation of caspase-3, it was obvious that compound 2h inhibited the proliferation of Jurkat cells through the mitochondrial apoptotic pathway. Other than this, compound 2h exerted inhibition effect to many other tumor cells and only showed weak cytotoxic to human normal cells suggesting that compound 2h possessed a broad range of anticancer spectrum and high safety to normal cells.
authors.affiliation: Key Lab of Industrial Fermentation Microbiology, Tianjin Key Lab of Industrial Microbiology, Sino-French Joint Lab of Food Nutrition/Safety and Medicinal Chemistry, Tianjin University of Science and Technology, Tianjin, 300457, PR China.
authors.forename: Yu-Ou
authors.initials: YO
authors.lastname: Teng
authors.affiliation: Key Lab of Industrial Fermentation Microbiology, Tianjin Key Lab of Industrial Microbiology, Sino-French Joint Lab of Food Nutrition/Safety and Medicinal Chemistry, Tianjin University of Science and Technology, Tianjin, 300457, PR China.
authors.forename: Hong-Ye
authors.initials: HY
authors.lastname: Zhao
authors.affiliation: Key Lab of Industrial Fermentation Microbiology, Tianjin Key Lab of Industrial Microbiology, Sino-French Joint Lab of Food Nutrition/Safety and Medicinal Chemistry, Tianjin University of Science and Technology, Tianjin, 300457, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Lab of Industrial Fermentation Microbiology, Tianjin Key Lab of Industrial Microbiology, Sino-French Joint Lab of Food Nutrition/Safety and Medicinal Chemistry, Tianjin University of Science and Technology, Tianjin, 300457, PR China.
authors.forename: Huan
authors.initials: H
authors.lastname: Liu
authors.affiliation: Key Lab of Industrial Fermentation Microbiology, Tianjin Key Lab of Industrial Microbiology, Sino-French Joint Lab of Food Nutrition/Safety and Medicinal Chemistry, Tianjin University of Science and Technology, Tianjin, 300457, PR China.
authors.forename: Mei-Le
authors.initials: ML
authors.lastname: Gao
authors.affiliation: Key Lab of Industrial Fermentation Microbiology, Tianjin Key Lab of Industrial Microbiology, Sino-French Joint Lab of Food Nutrition/Safety and Medicinal Chemistry, Tianjin University of Science and Technology, Tianjin, 300457, PR China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Key Lab of Industrial Fermentation Microbiology, Tianjin Key Lab of Industrial Microbiology, Sino-French Joint Lab of Food Nutrition/Safety and Medicinal Chemistry, Tianjin University of Science and Technology, Tianjin, 300457, PR China.
authors.forename: Kai-Lin
authors.initials: KL
authors.lastname: Han
authors.affiliation: Key Laboratory of Food Nutrition and Safety (Tianjin University of Science and Technology), Ministry of Education, Tianjin 300457, PR China.
authors.forename: Zhen-Chuan
authors.initials: ZC
authors.lastname: Fan
authors.affiliation: Université Pierre et Marie Curie-Paris 6, Institut Parisien de Chimie Moléculaire UMR CNRS 8232, 4 place Jussieu, 75005, Paris, France.
authors.forename: Yong-Min
authors.initials: YM
authors.lastname: Zhang
authors.affiliation: Key Lab of Industrial Fermentation Microbiology, Tianjin Key Lab of Industrial Microbiology, Sino-French Joint Lab of Food Nutrition/Safety and Medicinal Chemistry, Tianjin University of Science and Technology, Tianjin, 300457, PR China.
authors.forename: Hua
authors.initials: H
authors.lastname: Sun
authors.affiliation: Key Lab of Industrial Fermentation Microbiology, Tianjin Key Lab of Industrial Microbiology, Sino-French Joint Lab of Food Nutrition/Safety and Medicinal Chemistry, Tianjin University of Science and Technology, Tianjin, 300457, PR China. Electronic address: yupeng@tust.edu.cn.
authors.forename: Peng
authors.initials: P
authors.lastname: Yu
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007510:Isatin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D019169:Jurkat Cells; D015458:Leukemia, T-Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D007510:Isatin
keywords: Anti-tumor agents; Apoptosis; Isatin derivatives; Jurkat cells; Proliferation