Synthesis, DPPH Radical Scavenging, Cytotoxic Activity, and Apoptosis Induction Efficacy of Novel Thiazoles and Bis-thiazoles.

IF 1.7 4区化学 Q3 CHEMISTRY, ORGANIC

Current organic synthesis Pub Date : 2024-01-01 DOI:10.2174/0115701794264504231017113027

Amr Negm, Yasair S Al-Faiyz, Sayed M Riyadh, Abdelwahed R Sayed

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引用次数: 0

Abstract

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, in vitro antiproliferative, 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, 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.

Conclusion: Synthesis, DPPH Radical Scavenging, Cytotoxic activity, and Apoptosis Induction Efficacy based on Novel Thiazoles and Bis-thiazoles.

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新型噻唑和双噻唑的合成、DPPH自由基清除、细胞毒性和诱导细胞凋亡的功效。

背景：含有噻唑的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]二羟基-5-基）亚甲基）肼-1-甲硫酰胺与肼酰氯在二恶烷中反应，以三乙胺为碱性催化剂合成噻唑和双噻唑。测定了噻唑和双噻唑的抗氧化、体外抗增殖和细胞毒性作用。结果：以肼酰氯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-甲硫酰胺（1）在二恶烷中反应，以三乙胺为碱性催化剂，制备了新系列的5-甲基-2-（2-（6-硝基苯并[d][1.3]二氧环-5-基）亚甲）肼基-4-（芳基二氮杂环基）噻唑（4a-f）。按照相同的程序，通过分别使用摩尔比（1:2）的双腙酰氯（5、7和9）和硫代甲酰胺1，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结构的独特特征。评价了噻唑类和双噻唑类的抗氧化、体外抗增殖、细胞毒性和抗癌效果。化合物4d和4f是最有效的抗氧化剂。通过细胞凋亡标志物的基因表达和DNA片段分析，探讨合成产物的生化机制。噻唑类比双噻唑类更能显著抑制细胞生长和增殖。它们通过诱导凋亡基因P53的表达和下调抗凋亡基因Bcl-2的表达来诱导细胞凋亡。此外，它们在癌症细胞中诱导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剂，并且可以被认为是抗癌剂发现策略中的有效化合物。结论：新型噻唑和双噻唑的合成、DPPH自由基清除、细胞毒性和诱导细胞凋亡的功效。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current organic synthesis 化学-有机化学

CiteScore

3.40

自引率

5.60%

发文量

审稿时长

6-12 weeks

期刊介绍： Current Organic Synthesis publishes in-depth reviews, original research articles and letter/short communications on all areas of synthetic organic chemistry i.e. asymmetric synthesis, organometallic chemistry, novel synthetic approaches to complex organic molecules, carbohydrates, polymers, protein chemistry, DNA chemistry, supramolecular chemistry, molecular recognition and new synthetic methods in organic chemistry. The frontier reviews provide the current state of knowledge in these fields and are written by experts who are internationally known for their eminent research contributions. The journal is essential reading to all synthetic organic chemists. Current Organic Synthesis should prove to be of great interest to synthetic chemists in academia and industry who wish to keep abreast with recent developments in key fields of organic synthesis.