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Hybrid pharmacophore design and synthesis of isatin-benzothiazole analogs for their anti-breast cancer activity.

Abstract
A hybrid pharmacophore approach was used to design and synthesize isatin-benzothiazole analogs to examine their anti-breast cancer activity. The cytotoxicity of these compounds were determined using three different human breast tumor cell lines, MDA-MB231, MDA-MB468, MCF7, and two non-cancer breast epithelial cell lines, 184B5 and MCF10A. Although all compounds examined were quite effective on all the cancer cell lines examined, the compounds 4-bromo-1-diethylaminomethyl-1H-indole-2,3-dione (2l) and 4-chloro-1-dimethylaminomethyl-3-(6-methyl-benzothiazol-2-ylimino)-1,3-dihydro-indol-2-one (5e) emerged as the most active compounds of this series. Importantly, the cytotoxic effect of 2l was 10-15-fold higher on cancer than non-cancer cells, suggesting that this compound can be very effective for the control of breast cancer with low side effects. Since 2l showed effective cytotoxicity on MCF7 cells and arrested the cells at G2/M at a similar concentration, these two phenomena may be closely correlated. We conclude that the isatin-linked benzothiazole analog can serve as a prototype molecule for further development of a new class of anti-breast cancer agents.
AuthorsV Raja Solomon, Changkun Hu, Hoyun Lee
JournalBioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 17 Issue 21 Pg. 7585-92 (Nov 01 2009) ISSN: 1464-3391 [Electronic] England
PMID19804979 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • 4-bromo-1-diethylaminomethyl-1H-indole-2,3-dione
  • 4-chloro-1-dimethylaminomethyl-3-(6-methyl-benzothiazol-2-ylimino)-1,3-dihydro-indol-2-one
  • Antineoplastic Agents
  • Benzothiazoles
  • Indoles
  • Thiazoles
  • Isatin
  • benzothiazole
Topics
  • Antineoplastic Agents (chemical synthesis, chemistry, toxicity)
  • Benzothiazoles (chemistry)
  • Breast Neoplasms (drug therapy)
  • Drug Design
  • Drug Screening Assays, Antitumor
  • Female
  • Humans
  • Indoles (chemical synthesis, chemistry, toxicity)
  • Isatin (chemistry)
  • Thiazoles (chemical synthesis, chemistry, toxicity)

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