4.7 Article

New anticancer active and selective phenylene-bisbenzothiazoles: Synthesis, antiproliferative evaluation and DNA binding

期刊

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 63, 期 -, 页码 882-891

出版社

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2013.02.026

关键词

Amdino-substituted phenylene-bisbenzothiazoles; Antitumour evaluation; DNA-binding; Apoptosis

资金

  1. Croatian Ministry of Science Education and Sports [1170000000-3283, 335-0000000-3532, 335-0982464-239, 0982464-1356]
  2. Ligue Nationale Contre le Cancer (Comite du Nord, Septentrion)
  3. Association Laurette Fugain
  4. Association pour la Recherche sur le Cancer
  5. Institut pour la Recherche sur le Cancer de Lille (IRCL)
  6. CHRU de Lille
  7. Region Nord/Pas-de-Calais
  8. IRCL

向作者/读者索取更多资源

Novel amidino-derivatives of phenylene-bisbenzothiazoles were synthesized and tested for their anti-proliferative activity against several human cancer cell lines, as well as DNA-binding properties. The synthetic approach used for preparation of isomeric amidino substituted-phenylene-bis-benzothyazoles 3a-3f was achieved by condensation reaction of isophthaloyl dichloride 1a and terephthaloyl dichloride 1b or with phthalic acid 1c with 5-amidinium-2-aminobenzothiolate 2a and 5-(imidazolinium-2-yl)-2-aminobenzothiolate 2b in good yields. The targeted compounds were converted in the desired water soluble dihydrochloride salts by reaction of appropriate free base with concd HCl in ethanol or acetic acid. All tested compounds (3a-3f) showed antiproliferative effects on tumour cells in a concentration-dependant manner. The strongest activity and cytotoxicity was observed for diimidazolinyl substituted phenylene-bisbenzothiazole compound 3b. These effects were shown to be related to DNA-binding properties, topoisomerase I and II poisoning effects and apoptosis induction. The highest tested selectivity towards tumour cells was observed for the imidazolyl substituted phenylene-benzothiazole 3d that showed no cytotoxic effects on normal fibroblasts making it an excellent candidate for further chemical optimization and preclinical evaluation. (C) 2013 Elsevier Masson SAS. All rights reserved.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据