2. Academic Validation
  3. Synthesis and cytotoxic studies of novel 5-phenylisatin derivatives and their anti-migration and anti-angiogenic evaluation

Synthesis and cytotoxic studies of novel 5-phenylisatin derivatives and their anti-migration and anti-angiogenic evaluation

  • Eur J Med Chem. 2018 Aug 5:156:800-814. doi: 10.1016/j.ejmech.2018.07.032.
Qian Zhang 1,  Yuou Teng 1,  Yuan Yuan 1,  Tingting Ruan 1,  Qi Wang 1,  Xing Gao 1,  Yao Zhou 1,  Kailin Han 1,  Peng Yu 2,  Kui Lu 3
Affiliations

Affiliations

  • 1 China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, Tianjin University of Science and Technology, Tianjin, 300457, China.
  • 2 China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, Tianjin University of Science and Technology, Tianjin, 300457, China. Electronic address: yupeng@tust.edu.cn.
  • 3 China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, Tianjin University of Science and Technology, Tianjin, 300457, China. Electronic address: lukui@tust.edu.cn.
PMID: 30055465 DOI: 10.1016/j.ejmech.2018.07.032
Abstract

A number of 5-arylisatin derivatives were synthesized in 5-6 steps from readily available starting Materials. Their structures were confirmed by 1H NMR and 13C NMR as well as LC/MS. The cytotoxicity of these novel isatins against human leukemia K562 cells were evaluated by MTT assay in vitro. SAR studies indicated that the N-substituted benzyl and C-5 substituted phenyl groups greatly enhance their cytotoxic activity, whereas an intact carbonyl functionality on C-3 present in the parent ring is required to maintain such a potency. Particularly, N-(p-methoxybenzyl)-5-(p-methoxyphenyl)isatin (compound 2m) showed the highest antitumor activity against K562 cell lines (IC50 = 0.03 μM). Moreover, treatment with compound 2m significantly inhibited liver Cancer HepG2 cells proliferation and migration, which could also reduce the human umbilical vein endothelial cells (HUVEC) tube formation. In conclusion, compound 2m exhibited very good Cancer cells proliferation inhibition by angiogenesis responses in vitro, and 2m might be a promising angiogenesis inhibitor for Cancer treatment.

Keywords

5-phenylisatin; Angiogenesis; Migration; Proliferation; Synthesis.

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