In an effort to discover potential cytotoxic agents, a series of novel (Z)-5-((1,3-diphenyl-1H-pyrazol-4-yl)methylene)-3-((1-substituted phenyl-1H-1,2,3-triazol-4-yl)methyl)thiazolidine-2,4-dione derivatives (8a-n) were designed and synthesized in various steps with acceptable reaction procedures with quantitative yields and characterized by 1H NMR, 13C NMR, IR, HRMS and ESI-MS spectra. These newly synthesized novel derivatives were screened for their in vitro cell viability/cytotoxic studies against human breast cancer cell line (MCF-7) with various concentrations of 0.625 µM, 1.25 µM, 2.5 µM, 5 µM and 10 µM, respectively. The biological interpretation assay outcome was demonstrated in terms of cell viability percentage reduction and IC50 values against standard reference drug cisplatin. Based on these results, most of the derivatives exhibited promising cytotoxic activity. Among them, particularly compounds 8j (R1 = OMe and R3 = NO2) and 8e (R3 = CF3) demonstrate remarkable cytotoxic activity with IC50 values 0.426 µM ± 0.455 and 0.608 µM ± 0.408, which are even better than the standard drug cisplatin 0.636 µM ± 0.458 and compounds 8m (R2 = OMe and R3 = OMe) and 8c (R3 = OMe) exhibited closely equivalent IC50 values to the standard drug with IC50 values 0.95 µM ± 0.32 and 0.976 µM ± 0.313 and rest of the compounds exhibits moderate cytotoxic activity. Moreover, molecular modeling studies and ADME calculations of the novel synthesized derivatives are in adequate consent with the pharmacological screening results.

中文翻译：

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新型(Z)-5-((1,3-二苯基-1H-吡唑-4-基)亚甲基)-3-((1-取代苯基-1H-1,2,3-三唑-4)的设计与合成-基)甲基)噻唑烷-2,4-二酮：潜在的细胞毒性支架及其分子模型研究。


为了发现潜在的细胞毒剂，一系列新型 (Z)-5-((1,3-二苯基-1H-吡唑-4-基)亚甲基)-3-((1-取代的苯基-1H-1 ,2,3-三唑-4-基)甲基)噻唑烷-2,4-二酮衍生物(8a-n)是通过不同的步骤设计和合成的，具有可接受的反应程序和定量产率，并通过 1H NMR、13C NMR、IR 进行表征、HRMS 和 ESI-MS 谱图。这些新合成的新型衍生物分别以不同浓度0.625 µM、1.25 µM、2.5 µM、5 µM 和10 µM 进行了针对人乳腺癌细胞系(MCF-7) 的体外细胞活力/细胞毒性研究。生物学解释测定结果以细胞活力百分比降低和针对标准参考药物顺铂的 IC50 值来证明。基于这些结果，大多数衍生物表现出有希望的细胞毒活性。其中，特别是化合物8j（R1 = OMe和R3 = NO2）和8e（R3 = CF3）表现出显着的细胞毒活性，IC50值为0.426 µM ± 0.455和0.608 µM ± 0.408，甚至优于标准药物顺铂0.636 µM ± 0.458，化合物 8m（R2 = OMe 和 R3 = OMe）和 8c（R3 = OMe）表现出与标准药物非常相似的 IC50 值，IC50 值为 0.95 µM ± 0.32 和 0.976 µM ± 0.313，其余化合物表现出中等细胞毒性活动。此外，新型合成衍生物的分子模型研究和 ADME 计算与药理学筛选结果充分一致。