Yurttas Leyla, Ciftci Gulsen Akalin, Temel Halide Edip, Saglik Begum Nurpelin, Demir Bahar, Levent Serkan
Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Anadolu University, 26470 Eskisehir. Turkey.
Faculty of Pharmacy, Department of Biohemistry, Anadolu University, 26470 Eskisehir. Turkey.
Anticancer Agents Med Chem. 2017;17(13):1846-1853. doi: 10.2174/1871520617666170327151031.
Triazine ring is a prominent structural motif found in some azanucleosides whose efficiency improved many times in the research area of antitumor agents.
In this study, we have designed and synthesized novel 2-[(5,6-diphenyl-1,2,4-triazin-3-yl)thio]-N-(6- substituted benzo/(thiazol)-2-yl)acetamide (2a-d, 3a-f) derivatives using 1,2,4-triazine core along with two important heterocyles, thiazole and benzothiazole rings.
The acquired ten final compounds were screened to investigate their antitumor activity against lung adenocarcinoma cell line, A549 and mouse fibroblast cell line, NIH/3T3. Five compounds with higher antiproliferative activity have been further studied to evaluate whether the cell death due to necrosis or apoptosis using flow cytometry.
Compound 3b bearing 6-methylbenzothiazole moiety has been established as the most active antitumor compound with a selective profile and higher apoptotic cell level. All final componds were also screened against acetylcholine/butyrylcholinesterase enzymes to state their anticholinesterase activity.
三嗪环是在一些氮杂核苷中发现的显著结构基序，其在抗肿瘤药物研究领域的效率提高了许多倍。
在本研究中，我们使用1,2,4 - 三嗪核心以及噻唑和苯并噻唑环这两个重要的杂环设计并合成了新型2 - [(5,6 - 二苯基 - 1,2,4 - 三嗪 - 3 - 基)硫代] - N - (6 - 取代苯并/(噻唑) - 2 - 基)乙酰胺(2a - d，3a - f)衍生物。
对获得的十种最终化合物进行筛选，以研究它们对肺腺癌细胞系A549和小鼠成纤维细胞系NIH/3T3的抗肿瘤活性。对五种具有较高抗增殖活性的化合物进行了进一步研究，使用流式细胞术评估细胞死亡是由于坏死还是凋亡。
带有6 - 甲基苯并噻唑部分的化合物3b已被确定为最具活性的抗肿瘤化合物，具有选择性特征和较高的凋亡细胞水平。所有最终化合物还针对乙酰胆碱/丁酰胆碱酯酶进行了筛选，以表明它们的抗胆碱酯酶活性。
