Synthesis and antiproliferative evaluation of some new amidino-substituted bis-benzothiazolyl-pyridines and pyrazine
Synthesis and antiproliferative evaluation of some new amidino-substituted bis-benzothiazolyl-pyridines and pyrazine
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DOI：
10.1016/j.ejmech.2012.07.005
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发表时间：
2012-09-01
影响因子：
6.7
通讯作者：
Karminski-Zamola, Grace
中科院分区：
文献类型：
--
作者：
Racane, Livio;Pavelic, Sandra Kraljevic;Karminski-Zamola, Grace
合成了新的二胺取代的双苯并噻唑基吡啶和吡嗪的构象受限衍生物，并测定了它们对几种人癌细胞株的抗增殖活性。以2-咪唑基取代的2-氨基硫酚2b和2-咪唑基取代的2-氨基硫酚2b为原料，在多聚磷酸中进行缩合反应，合成了氨基苯并噻唑二取代吡啶3a-3k和吡嗪31。大大优化了缩合反应。通过适当的游离碱与氯化氢在乙醇或醋酸中反应，目标化合物被转化为所需的水溶性二盐酸盐。抗增殖实验表明，二胺基衍生物和二咪唑啉基衍生物的抗增殖活性有显著差异，后者对受试肿瘤细胞株具有更强的浓度依赖性抗增殖作用，因此是进一步化学优化和生物学研究的重要化合物类。对SW620细胞和BJ成纤维细胞进行的双咪唑基衍生物3b的生物学研究表明，氧化应激可能是抗增殖作用的机制，并预测了这类化合物的抗肿瘤特性。(C)2012年爱思唯尔·马森公司。版权所有。
Novel diamidino substituted conformationally restricted derivatives of bis-benzothiazolyl-pyridines and pyrazine were synthesized and their antiproliferative activity against several human cancer cell lines were determinated. The synthetic approach used for preparation of isomeric amidinobenzotiazolyl disubstituted pyridines 3a-3k and pyrazine 31 was achieved by condenzation reaction of commercially available pyridine and pyrazine dicarboxylic acids with amidino- 2a and 2-imidazolinyl-substituted 2-aminothiophenol 2b in polyphosphoric acid in moderate to good yield. The condenzation reaction was greatly optimized. 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. Antiproliferative assays revealed significant differences in antiproliferative activities of diamidino- and diimidazolinyl-derivatives, the latter exerting stronger concentration-dependent antiproliferative effects on tested tumor cell lines and thus being a prominent compound class for further chemical optimization and biological studies. Biological studies on SW620 cell line and BJ fibroblasts performed for the diimidazolinyl-derivative 3b revealed oxidative stress as a possible mechanism of antiproliferative action and predicted antineoplastic properties for this class of compounds. (C) 2012 Elsevier Masson SAS. All rights reserved.