Department of Chemistry, College of Science, King Faisal University, Al-Ahsa, 31982, Saudi Arabia.
Chemistry Department, Faculty of Science, Mansoura University, Mansoura, 35516, Egypt.
Curr Org Synth. 2024;21(8):1081-1090. doi: 10.2174/0115701794264504231017113027.
Heterocyclic materials-containing thiazoles exhibited incredible importance in pharmaceutical chemistry and drug design due to their extensive biological properties.
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, antiproliferative, and cytotoxicity efficacy of thiazoles and bis-thiazoles were measured.
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 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, in vitro 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.
Synthesis, DPPH Radical Scavenging, Cytotoxic activity, and Apoptosis Induction Efficacy based on Novel Thiazoles and Bis-thiazoles.
含噻唑的杂环材料由于其广泛的生物特性，在药物化学和药物设计中具有重要意义。
在二氧六环中并在三乙胺作为碱性催化剂的存在下，由 2-((6-硝基苯并[d][1,3]二恶唑-5-基)亚甲基)肼-1-碳硫酰胺与酰肼酰氯反应合成噻唑和双噻唑。测量噻唑和双噻唑的抗氧化、抗增殖和细胞毒性作用。
在这项工作中，通过将酰肼酰氯 2a-f 与 2-((6-硝基苯并[d][1,3]二恶唑-5-基)亚甲基)肼-1-碳硫酰胺（1）在二氧六环中反应，以三乙胺作为碱性催化剂，制备了一系列新型的 5-甲基-2-((6-硝基苯并[d][1,3]二恶唑-5-基)亚甲基)肼基-4-(芳基亚氨基)噻唑（4a-f）。通过利用双酰肼酰氯（5、7 和 9）和碳硫酰胺 1（摩尔比为 1:2），按照相同的程序合成了双噻唑（6、8 和 10）。通过光谱工具和元素分析阐明了分离产物的结构特征。评价了噻唑和双噻唑的抗氧化、体外抗增殖、细胞毒性和抗癌活性。化合物 4d 和 4f 是最有效的抗氧化剂。评估了凋亡标记物的基因表达和 DNA 的片段化分析，以探索合成产物的生化机制。噻唑类显著抑制细胞生长和增殖，优于双噻唑类。它们通过诱导凋亡基因表达 P53 和下调抗凋亡基因表达 Bcl-2 诱导细胞凋亡。此外，它们诱导癌细胞中 DNA 的片段化，表明它们可以通过抑制肿瘤生长和进展作为抗癌剂，并且可以被认为是抗癌剂发现策略中的有效化合物。
新型噻唑和双噻唑的合成、DPPH 自由基清除、细胞毒性活性和诱导凋亡作用。
