含 S - 烷基/芳基的一些新型咪唑并[1,2- a ]吡啶杂环的合成与抗癌活性评估

IF 1.4 4区 化学 Q4 CHEMISTRY, INORGANIC & NUCLEAR
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引用次数: 0

摘要

在此,我们报告了 14 种含有 S-烷基/芳基的新型咪唑并[1,2-a]吡啶衍生物 (6a-6n) 的合成和抗癌活性。目标化合物通过六步合成路线获得。起始原料为 1-(4-氨基苯基)乙-1-酮。在最后一步,2-氯-N-[4-(咪唑并[1,2-a]吡啶-2-基)苯基]乙酰胺(5)与各种脂肪族/芳香族硫醇衍生物发生反应,得到最终化合物 6a-6n。评估了这些化合物对 A549(人非小细胞肺癌)、C6(大鼠神经胶质瘤)、MCF-7(人乳腺癌)和 HepG2(人肝癌)肿瘤细胞以及 NIH/3T3(小鼠胚胎成纤维细胞)健康细胞的细胞毒性。第一步 MTT 试验表明,化合物 6a、6d、6e 和 6i 对所有测试的肿瘤细胞株都具有抗增殖活性。第二步的 BrdU 细胞增殖测定和流式细胞仪分析表明,化合物 6d 和 6i 通过凋亡途径抑制了 HepG2 细胞系的 DNA 合成,且具有时间依赖性。化合物 6d 和 6i 与 caspase-3 和 caspase-9 的分子对接研究表明,它们与酶的活性位点有结合作用,这证实了实验结果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Synthesis and anticancer activity evaluation of some novel imidazo[1,2-a]pyridine based heterocycles containing S-alkyl/aryl moiety

Here we report the synthesis and anticancer activities of fourteen novel imidazo[1,2-a]pyridine derivatives (6a-6n) containing S-alkyl/aryl moiety. The target compounds were obtained via a six-step synthetic route. 1-(4-Aminophenyl)ethan-1-one was the starting material. In the last step, 2-chloro-N-[4-(imidazo[1,2-a]pyridin-2-yl)phenyl]acetamide (5) was allowed to react with various aliphatic/aromatic thiol derivatives, affording the final compounds 6a-6n. The cytotoxicity of the compounds was evaluated against A549 (human non-small cell lung cancer), C6 (rat glioma), MCF-7 (human breast carcinoma) and HepG2 (human liver carcinoma) tumor cells and NIH/3T3 (mouse embryonic fibroblast cells) healthy cells. First step MTT assay reported that compounds 6a, 6d, 6e and 6i exhibited antiproliferative activity against all tested tumor lines. Second step BrdU cell proliferation assay and flow cytometric analysis revealed that compounds 6d and 6i inhibited DNA synthesis on HepG2 cell line time-dependently by apoptotic pathway. Molecular docking study of compounds 6d and 6i with caspase-3 and caspase-9 revealed their binding interactions with the enzyme’s active site, confirming the experimental findings.

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来源期刊
CiteScore
2.60
自引率
7.70%
发文量
103
审稿时长
2.1 months
期刊介绍: Phosphorus, Sulfur, and Silicon and the Related Elements is a monthly publication intended to disseminate current trends and novel methods to those working in the broad and interdisciplinary field of heteroatom chemistry.
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