Novel thiazole-based cyanoacrylamide derivatives: DNA cleavage, DNA/BSA binding properties and their anticancer behaviour against colon and breast cancer cells

IF 4.3 2区化学 Q2 CHEMISTRY, MULTIDISCIPLINARY BMC Chemistry Pub Date : 2024-09-20 DOI:10.1186/s13065-024-01284-2

Karim Barakat, Mohamed A. Ragheb, Marwa H. Soliman, Amr M. Abdelmoniem, Ismail A. Abdelhamid

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Abstract

A novel series of 2-cyano-3-(pyrazol-4-yl)-N-(thiazol-2-yl)acrylamide derivatives (3a–f) were synthesized using Knoevenagel condensation and characterized using various spectral tools. The weak nuclease activity of compounds (3a–f) against pBR322 plasmid DNA was greatly enhanced by irradiation at 365 nm. Compounds 3b and 3c, incorporating thienyl and pyridyl moieties, respectively, exhibited the utmost nuclease activity in degrading pBR322 plasmid DNA through singlet oxygen and superoxide free radicals’ species. Furthermore, compounds 3b and 3c affinities towards calf thymus DNA (CT-DNA) and bovine serum albumin (BSA) were investigated using UV–Vis and fluorescence spectroscopic analysis. They revealed good binding characteristics towards CT-DNA with K_b values of 6.68 × 10⁴ M⁻¹ and 1.19 × 10⁴ M⁻¹ for 3b and 3c, respectively. In addition, compounds 3b and 3c ability to release free radicals on radiation were targeted to be used as cytotoxic compounds in vitro for colon (HCT116) and breast cancer (MDA-MB-231) cells. A significant reduction in the cell viability on illumination at 365 nm was observed, with IC₅₀ values of 23 and 25 µM against HCT116 cells, and 30 and 9 µM against MDA-MB-231 cells for compounds 3b and 3c, respectively. In conclusion, compounds 3b and 3c exhibited remarkable DNA cleavage and cytotoxic activity on illumination at 365 nm which might be associated with free radicals’ production in addition to having a good affinity for interacting with CT-DNA and BSA.

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新型噻唑基氰基丙烯酰胺衍生物：DNA 裂解、DNA/BSA 结合特性及其对结肠癌和乳腺癌细胞的抗癌作用

利用 Knoevenagel 缩合法合成了一系列新型 2-氰基-3-(吡唑-4-基)-N-(噻唑-2-基)丙烯酰胺衍生物 (3a-f)，并利用各种光谱工具对其进行了表征。化合物（3a-f）对 pBR322 质粒 DNA 的弱核酸酶活性在 365 纳米波长的照射下大大增强。化合物 3b 和 3c 分别含有噻吩基和吡啶基，在通过单线态氧和超氧自由基物种降解 pBR322 质粒 DNA 时表现出最强的核酸酶活性。此外，化合物 3b 和 3c 对小牛胸腺 DNA（CT-DNA）和牛血清白蛋白（BSA）的亲和力也通过紫外可见光谱和荧光光谱分析进行了研究。结果表明，化合物 3b 和 3c 与 CT-DNA 具有良好的结合特性，其 Kb 值分别为 6.68 × 104 M-1 和 1.19 × 104 M-1。此外，化合物 3b 和 3c 还具有在辐射中释放自由基的能力，因此可用作结肠癌（HCT116）和乳腺癌（MDA-MB-231）细胞的体外细胞毒性化合物。化合物 3b 和 3c 在 365 纳米波长的照射下细胞活力明显降低，对 HCT116 细胞的 IC50 值分别为 23 µM 和 25 µM，对 MDA-MB-231 细胞的 IC50 值分别为 30 µM 和 9 µM。总之，化合物 3b 和 3c 在 365 纳米波长的光照下表现出显著的 DNA 裂解和细胞毒性活性，这可能与自由基的产生有关，此外，它们还与 CT-DNA 和 BSA 具有良好的亲和力。

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来源期刊

BMC Chemistry Chemistry-General Chemistry

CiteScore

5.30

自引率

2.20%

发文量

审稿时长

27 weeks

期刊介绍： BMC Chemistry, formerly known as Chemistry Central Journal, is now part of the BMC series journals family. Chemistry Central Journal has served the chemistry community as a trusted open access resource for more than 10 years – and we are delighted to announce the next step on its journey. In January 2019 the journal has been renamed BMC Chemistry and now strengthens the BMC series footprint in the physical sciences by publishing quality articles and by pushing the boundaries of open chemistry.