Design, synthesis and biological evaluation of novel 4-thiazolidinones containing indolin-2-one moiety as potential antitumor agent

Eur J Med Chem. 2011 Aug;46(8):3509-18. doi: 10.1016/j.ejmech.2011.05.017. Epub 2011 May 13.

Abstract

A series of novel 4-thiazolidinone and indolin-2-one hybrid derivatives 5a-5s and 10a-10s have been designed and synthesized and their cytotoxic activities were evaluated in vitro against three human cancer cell lines including HT-29 (human colon cancer), H460 (human lung cancer), MDA-MB-231 (human breast cancer) by MTT assay. Several potent target compounds (5m, 5p, 5s, 10a, 10c-10g, 10m, 10p) were further evaluated against one cancer cell line SMMC-7721 (human liver cancer) and one normal cell line WI-38 (human fetal lung fibroblasts). Most of the prepared compounds exhibited significant antitumor activities against different human cancer cell lines. Compound 10c (IC(50) = 0.025 μM, 0.075 μM, 0.77 μM, 1.95 μM) was 52, 36, 4.8 and 3.3 times more active than Sunitinib (IC(50) = 1.3 μM, 2.7 μM, 3.7 μM, 6.47 μM) against HT-29, H460, MDA-MB-231 and SMMC-7721 cancer cell line, respectively.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / pathology
  • Drug Design
  • Drug Screening Assays, Antitumor
  • Female
  • Fibroblasts / cytology
  • Fibroblasts / drug effects*
  • Humans
  • Indoles / chemistry*
  • Indoles / pharmacology
  • Inhibitory Concentration 50
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / pathology
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / pathology
  • Pyrroles / pharmacology
  • Sunitinib
  • Thiazolidines / chemical synthesis*
  • Thiazolidines / pharmacology

Substances

  • Antineoplastic Agents
  • Indoles
  • Pyrroles
  • Thiazolidines
  • indolin-2-one
  • Sunitinib