title: Design, synthesis and in vitro cytotoxicity evaluation of 5-(2-carboxyethenyl)isatin derivatives as anticancer agents.
abstract: Forty four di- or trisubstituted novel isatin derivatives were designed and synthesized in 5-6 steps in 25-45% overall yields. Their structures were confirmed by (1)H NMR and (13)C NMR as well as LC-MS. The anticancer activity of these new isatin derivatives against three human tumor cell lines, K562, HepG2 and HT-29, were evaluated by MTT assay in vitro. SAR studies suggested that the combination of 1-benzyl and 5-[trans-2-(methoxycarbonyl)ethen-1-yl] substitution greatly enhance their cytotoxic activity, whereas an intact carbonyl functionality on C-3 as present in the parent ring is required to such a potency. This study leads to the identification of two highly active molecules, compounds 2h (IC50=3 nM) and 2k (IC50=6 nM), against human leukemia K562 cells.
authors.affiliation: Key Laboratory of Industrial Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China; Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China.
authors.forename: Kailin
authors.initials: K
authors.lastname: Han
authors.affiliation: Key Laboratory of Industrial Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China; Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Industrial Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China; Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China.
authors.forename: Fengxi
authors.initials: F
authors.lastname: Liu
authors.affiliation: Key Laboratory of Industrial Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China; Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China.
authors.forename: Qiannan
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Key Laboratory of Industrial Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China; Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Wang
authors.affiliation: Key Laboratory of Industrial Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China; Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Key Laboratory of Industrial Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China; Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China.
authors.forename: Binbin
authors.initials: B
authors.lastname: Song
authors.affiliation: College of Sciences, Tianjin University of Science and Technology, Tianjin 300457, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Chemo Dynamics, Inc., 3 Crossman Road South, Sayreville, NJ 08872, USA.
authors.forename: Qingwei
authors.initials: Q
authors.lastname: Yao
authors.affiliation: Key Laboratory of Industrial Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China; Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China. Electronic address: tyo201485@tust.edu.cn.
authors.forename: Yuou
authors.initials: Y
authors.lastname: Teng
authors.affiliation: Key Laboratory of Industrial Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China; Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, 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 / Q000138:chemical synthesis* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D003603:Cytotoxins / Q000138:chemical synthesis* / Q000494:pharmacology; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D019073:HT29 Cells; D056945:Hep G2 Cells; D006801:Humans; D020014:K562 Cells
chemical_list: D000970:Antineoplastic Agents; D003603:Cytotoxins
keywords: Antitumor activity; In vitro cytotoxicity; Isatin derivatives