Breast cancer is a serious threat to the health and lives of women. Two novel series of N′-(2-oxoindolin-3-ylidene)-6-methylimidazo[2,1-b]thiazole-5-carbohydrazides and 1-(aryl)-3-(6-methylimidazo[2,1-b]thiazol-5-yl)ureas were designed, synthesized and investigated for their anticancer efficacy against the MCF-7 breast cell line. Three compounds of the first series showed potent activity toward MCF-7 with IC50 in the range 8.38–11.67 µM, respectively, as compared to Sorafenib (IC50 = 7.55 µM). N′-(1-butyl-2-oxoindolin-3-ylidene)-6-methylimidazo[2,1-b]thiazole-5-carbohydrazide inhibited VEGFR-2 with IC50 = 0.33 µM when compared with Sorafenib (IC50 = 0.09 µM). Furthermore, this compound was introduced to PCR assessment, where it increased Bax, caspase 8, caspase 9 and cytochrome C levels by 4.337-, 2.727-, 4.947- and 2.420-fold, respectively, while it decreased levels of Bcl-2, as the anti-apoptotic gene, by 0.359-fold when compared to the untreated control MCF-7. This compound was also arrested in the G2/M phase by 27.07%, compared with 11.31% for the control MCF-7. Furthermore, it induced early and late apoptosis in MCF-7. In addition, a molecular docking study in the VEGFR-2 active site was performed to assess the binding profile for the most active compounds. Moreover, ADME parameters of the targeted compounds were also evaluated.

中文翻译：

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N'-(2-Oxoindolin-3-ylidene)-6-甲基咪唑并[2,1-b]噻唑-5-碳酰肼作为 MCF-7 乳腺癌潜在抗增殖剂的设计、合成和生物学评估


乳腺癌严重威胁女性的健康和生命。 N'-(2-氧代吲哚啉-3-亚基)-6-甲基咪唑并[2,1-b]噻唑-5-碳酰肼和1-(芳基)-3-(6-甲基咪唑[2,1-]的两个新系列b]噻唑-5-基)脲被设计、合成并研究其对MCF-7乳腺细胞系的抗癌功效。第一个系列的三种化合物对 MCF-7 显示出有效的活性，与索拉非尼 (IC50 = 7.55 µM) 相比，IC50 范围分别为 8.38–11.67 µM。与索拉非尼相比，N'-(1-丁基-2-氧吲哚啉-3-亚基)-6-甲基咪唑并[2,1-b]噻唑-5-碳酰肼抑制 VEGFR-2，IC50 = 0.33 µM (IC50 = 0.09 µM) ）。此外，该化合物被引入 PCR 评估中，它使 Bax、caspase 8、caspase 9 和细胞色素 C 的水平分别增加了 4.337、2.727、4.947 和 2.420 倍，同时降低了 Bcl-2 的水平，如下所示与未处理的对照MCF-7相比，抗凋亡基因增加了0.359倍。该化合物在 G2/M 期也被抑制了 27.07%，而对照 MCF-7 则为 11.31%。此外，它还诱导 MCF-7 的早期和晚期细胞凋亡。此外，还对 VEGFR-2 活性位点进行了分子对接研究，以评估最活跃化合物的结合特征。此外，还评估了目标化合物的 ADME 参数。