Background:: Heterocyclic materials-containing thiazoles exhibited incredible importance in pharmaceutical chemistry and drug design due to their extensive biological properties. Methods:: Synthesis of thiazoles and bis-thiazoles from the reaction of 2-((6-Nitrobenzo[ d][1,3]dioxol-5-yl)methylene)hydrazine-1-carbothioamide with hydrazonoyl chlorides in dioxane and in the existence of triethylamine as basic catalyst. The antioxidant, invitro anti-proliferative, and cytotoxicity efficacy of thiazoles and bis-thiazoles were measured. Results:: In this work, novel series of 5-methyl-2-(2-(-(6-nitrobenzo[d][1,3]dioxol-5-yl)methylene) hydrazinyl)-4-(aryldiazenyl)thiazoles (4a-f) were prepared via the reaction of hydrazonoyl chlorides 2a-f with 2-((6-nitrobenzo[d][1,3]dioxol-5-yl)methylene)hydrazine-1-carbothioamide (1) in dioxane and employing triethylamine as basic catalyst. Following the same procedure, bisthiazoles (6, 8, and 10) have been synthesized by utilizing bis-hydrazonoyl chlorides (5, 7, and 9) and carbothioamide 1 in a molar ratio (1:2), respectively. The distinctive features in the structure of isolated products were elucidated by spectroscopic tools and elemental analyses. The antioxidant, invitro anti-proliferative, cytotoxicity, and anti-cancer efficacy of thiazoles and bis-thiazoles were evaluated. Compounds 4d and 4f were the most potent antioxidant agents. Gene expression of apoptosis markers and fragmentation assay of DNA were assessed to explore the biochemical mechanism of synthesized products. Thiazoles significantly inhibited cell growth and proliferation more than bis-thiazoles. They induced apoptosis through induction of apoptotic gene expression P53 and downregulation of antiapoptotic gene expression Bcl-2. Moreover, they induced fragmentation of DNA in cancer cells, indicating that they could be employed as anticancer agents by inhibiting tumor growth and progression and can be considered effective compounds in the strategy of anti-cancer agents’ discovery. Conclusion:: Synthesis, DPPH Radical Scavenging, Cytotoxic activity, and Apoptosis Induction Efficacy based on Novel Thiazoles and Bis-thiazoles.

中文翻译：

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新型噻唑和双噻唑的合成、DPPH自由基清除、细胞毒活性和细胞凋亡诱导功效

背景：含噻唑杂环材料由于其广泛的生物学特性，在药物化学和药物设计中表现出令人难以置信的重要性。方法:: 2-((6-硝基苯并[d][1,3]间二氧杂环戊醇-5-基)亚甲基)肼-1-硫代硫酰胺与亚肼酰氯在二氧六环和水中反应合成噻唑和双噻唑三乙胺作为碱性催化剂存在。测量了噻唑和双噻唑的抗氧化、体外抗增殖和细胞毒性功效。结果:: 在这项工作中，新系列的 5-甲基-2-(2-(-(6-硝基苯并[d][1,3]间二氧醇-5-基)亚甲基)肼基)-4-(芳基二氮烯基)噻唑(4a-f)是通过亚肼酰氯2a-f与2-((6-硝基苯并[d][1,3]二氧杂环戊醇-5-基)亚甲基)肼-1-硫代硫酰胺(1)在二恶烷中反应制备采用三乙胺作为碱性催化剂。按照相同的步骤，分别利用双亚肼酰氯(5、7和9)和硫硫脲1以摩尔比(1:2)合成双噻唑(6、8和10)。通过光谱工具和元素分析阐明了分离产物结构的独特特征。评估了噻唑和双噻唑的抗氧化、体外抗增殖、细胞毒性和抗癌功效。化合物4d和4f是最有效的抗氧化剂。通过评估凋亡标志物的基因表达和DNA片段化分析来探索合成产物的生化机制。噻唑类药物比双噻唑类药物更能显着抑制细胞生长和增殖。它们通过诱导凋亡基因 P53 表达和下调抗凋亡基因 Bcl-2 表达来诱导细胞凋亡。此外，它们在癌细胞中诱导DNA断裂，表明它们可以通过抑制肿瘤生长和进展而用作抗癌药物，并且可以被认为是抗癌药物发现策略中的有效化合物。结论:: 基于新型噻唑类和双噻唑类的合成、DPPH 自由基清除、细胞毒活性和细胞凋亡诱导功效。