{"title":"Synthesis and anticancer activity evaluation of some novel imidazo[1,2-a]pyridine based heterocycles containing S-alkyl/aryl moiety","authors":"","doi":"10.1080/10426507.2024.2349305","DOIUrl":null,"url":null,"abstract":"<div><p>Here we report the synthesis and anticancer activities of fourteen novel imidazo[1,2-<em>a</em>]pyridine derivatives (<strong>6a</strong>-<strong>6n</strong>) containing <em>S</em>-alkyl/aryl moiety. The target compounds were obtained <em>via</em> a six-step synthetic route. 1-(4-Aminophenyl)ethan-1-one was the starting material. In the last step, 2-chloro-<em>N</em>-[4-(imidazo[1,2-<em>a</em>]pyridin-2-yl)phenyl]acetamide (<strong>5</strong>) was allowed to react with various aliphatic/aromatic thiol derivatives, affording the final compounds <strong>6a</strong>-<strong>6n</strong>. 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 <strong>6a, 6d, 6e</strong> and <strong>6i</strong> exhibited antiproliferative activity against all tested tumor lines. Second step BrdU cell proliferation assay and flow cytometric analysis revealed that compounds <strong>6d</strong> and <strong>6i</strong> inhibited DNA synthesis on HepG2 cell line time-dependently by apoptotic pathway. Molecular docking study of compounds <strong>6d</strong> and <strong>6i</strong> with caspase-3 and caspase-9 revealed their binding interactions with the enzyme’s active site, confirming the experimental findings.</p></div>","PeriodicalId":20056,"journal":{"name":"Phosphorus, Sulfur, and Silicon and the Related Elements","volume":null,"pages":null},"PeriodicalIF":1.4000,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Phosphorus, Sulfur, and Silicon and the Related Elements","FirstCategoryId":"92","ListUrlMain":"https://www.sciencedirect.com/org/science/article/pii/S1042650724000236","RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"CHEMISTRY, INORGANIC & NUCLEAR","Score":null,"Total":0}
引用次数: 0
Abstract
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.
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.