Abstract

A series of new thiazole incorporated pyridine derivatives containing the phenoxyacetamide moiety as a linking bridge has been synthesized. The synthetic strategy involves condensation of 2-(4-formylphenoxy)-N-(thiazol-2-yl)acetamide with cyanoacetic hydrazide followed by heterocyclization with acetylacetone, treatment of the produced acrylamides with malononitrile and substituted acetophenones, then heating the generated chalcones with mononitrile in acetic acid and ammonium acetate. In vitro anticancer activity of the newly synthesized thiazole-pyridine hybrids has been evaluated against prostate (PC3), liver (HepG2), laryngeal (Hep-2), and breast (MCF-7) cancer cell lines. One of thiazole-pyridine compounds 8c demonstrates higher activity (IC₅₀ 5.71 μM) against breast cancer than 5-fluorouracil used as a reference (IC₅₀ 6.14 μM). Molecular docking procedure has provided valuable information on the binding sites of the synthesized compounds with rho-associated protein kinase 1 (ROCK-1).

中文翻译：

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新型噻唑-吡啶杂化物的合成及其抗癌活性

摘要

已经合成了一系列新的并入噻唑的吡啶衍生物，它们含有苯氧基乙酰胺部分作为连接桥。合成策略包括将2-（4-甲酰基苯氧基）-N-（噻唑-2-基）乙酰胺与氰基乙酰肼缩合，然后用乙酰丙酮杂环化，用丙二腈和取代的苯乙酮处理生成的丙烯酰胺，然后将生成的查耳酮与在乙酸和乙酸铵中的单腈。新合成的噻唑-吡啶杂化物的体外抗癌活性已针对前列腺癌（PC3），肝癌（HepG2），喉癌（Hep-2）和乳腺癌（MCF-7）进行了评估。噻唑吡啶化合物8c之一显示出更高的活性（IC ₅₀5.71μM）比使用5-氟尿嘧啶作为参考（IC ₅₀ 6.14μM）。分子对接程序已经提供了有关合成化合物与rho相关蛋白激酶1（ROCK-1）的结合位点的有价值的信息。