2. Academic Validation
  3. Design, synthesis and in vitro cytotoxicity evaluation of 5-(2-carboxyethenyl)isatin derivatives as anticancer agents

Design, synthesis and in vitro cytotoxicity evaluation of 5-(2-carboxyethenyl)isatin derivatives as anticancer agents

  • Bioorg Med Chem Lett. 2014 Jan 15;24(2):591-4. doi: 10.1016/j.bmcl.2013.12.001.
Kailin Han 1,  Yao Zhou 1,  Fengxi Liu 1,  Qiannan Guo 1,  Pengfei Wang 1,  Yao Yang 1,  Binbin Song 1,  Wei Liu 2,  Qingwei Yao 3,  Yuou Teng 4,  Peng Yu 5
Affiliations

Affiliations

  • 1 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.
  • 2 College of Sciences, Tianjin University of Science and Technology, Tianjin 300457, PR China.
  • 3 Chemo Dynamics, Inc., 3 Crossman Road South, Sayreville, NJ 08872, USA.
  • 4 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.
  • 5 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.
PMID: 24360564 DOI: 10.1016/j.bmcl.2013.12.001
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.

Keywords

Antitumor activity; In vitro cytotoxicity; Isatin derivatives.

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