A new series of skeletons 2-(morpholinoimino)-4,5-disubstituted-3- phenylthiazoles (2-15) was synthesized. The methodology involved the reactions of 1- morpholino-3-phenyl-thiourea (1) with a variety of α-halocarbonyl compounds under Hantzsch reaction conditions. The reaction mechanism for some postulated routes was modeled using quantum mechanical calculations in order to investigate the regioselectivity preference of this reaction in terms of thermodynamics. The quantum mechanical computations compiled with experimental IR, 1H- and 13C-NMR spectral analysis supported the favorable product, which has a thiazole ring bearing the morpholinoimino moiety at position C−2. All synthesized products were screened using the sulforhodamine B (SRB) assay for their cytotoxic properties against various cancer cell lines. Fortunately, the target compounds 2, 4, 5, 6, 11, and 12 were discovered to be comparable to doxorubicin in terms of their potency against all evaluated cell lines. Utilizing flow cytometry, apoptosis and cell cycle analyses were determined and supported by molecular docking studies. All tumor cells were significantly early- and late-apoptotic affected by the products 2, 4, 5, 6, 11 and 12, and these products also significantly halted all studied types of cancer cells in both S and G2 phases. The discovered compounds 2 and 12 were then subjected to a molecular docking experiment to examine how they bind with the VEGFR-2-KDR receptor.

中文翻译：

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新型功能化吗啉噻唑衍生物：区域选择性合成、计算研究、抗癌活性评价和分子对接研究

合成了一系列新的骨架2-(吗啉代亚氨基)-4,5-二取代-3-苯基噻唑(2-15)。该方法涉及 1-吗啉代-3-苯基-硫脲 (1) 与各种 α-卤代羰基化合物在 Hantzsch 反应条件下的反应。使用量子力学计算对一些假设路线的反应机理进行建模，以研究该反应在热力学方面的区域选择性偏好。与实验 IR、1H 和 13C-NMR 光谱分析相结合的量子力学计算支持了有利的产物，该产物具有在 C−2 位上带有吗啉代亚氨基部分的噻唑环。所有合成产品均使用磺基罗丹明 B (SRB) 测定筛选其针对各种癌细胞系的细胞毒性特性。幸运的是，我们发现目标化合物 2、4、5、6、11 和 12 在对抗所有评估细胞系的效力方面与阿霉素相当。利用流式细胞术、分子对接研究确定并支持细胞凋亡和细胞周期分析。所有肿瘤细胞均受到产品 2、4、5、6、11 和 12 的显着早期和晚期凋亡影响，并且这些产品还显着阻止所有研究类型的癌细胞处于 S 期和 G2 期。然后对发现的化合物2和12进行分子对接实验，以检查它们如何与VEGFR-2-KDR受体结合。