4-Thiazolidinones and phenylaminopyrimidines are known as anticancer agents. Imatinib is the pioneer phenylaminopyrimidine derivative kinase inhibitor, which is used for the treatment of chronic myeloid leukemia. With a hybrid approach, a novel series of 5-benzylidene-2-arylimino-4-thiazolidinone derivatives containing phenylaminopyrimidine core were designed, synthesized, and tested for their anticancer activity on K562 (chronic myeloid leukemia), PC3 (prostat cancer), and SHSY-5Y (neuroblastoma) cells. Since superior anticancer activity was observed on K562 cells, further biological studies of selected compounds (8, 15, and 34) were performed on K562 cells. For the synthesis of designed compounds, thiourea compounds were converted to 2-imino-1,3-thiazolidin-4-ones with α-chloroacetic acid in the presence of sodium acetate. 5-Benzylidene-2-imino-1,3-thiazolidin-4-one derivatives were obtained by Knoevenagel condensation of 2-imino-1,3-thiazolidin-4-ones with related aldehydes. Compounds 8, 15, and 34 were evaluated for cell viability, apoptosis studies, cell cycle experiments, and DNA damage assays. IC50 values of compounds 8, 15, and 34 were found as 5.26 ± 1.03, 3.52 ± 0.91, and 8.16 ± 1.27 μM, respectively, in K562 cells. Preferably, these compounds showed less toxicity towards L929 cells compared to imatinib. Furthermore, compounds 8 and 15 significantly induced early and late apoptosis in a time-dependent manner. Compounds 15 and 34 induced cell cycle arrest at G0/G1 phase and compound 8 caused cell cycle arrest at G2/M phase. Based on DNA damage assay, compounds 8 and 15 were found to be more genotoxic than imatinib towards K562 cells. To put more molecular insight, possible Abl inhibition mechanisms of most active compounds were predicted by molecular docking studies. In conclusion, a novel series of 5-benzylidene-2-arylimino-4-thiazolidinone derivatives and their promising anticancer activities were reported herein.

中文翻译：

---

新型 4-噻唑烷酮-苯基氨基嘧啶杂化物的设计、合成和抗癌活性。

4-噻唑烷酮和苯氨基嘧啶被称为抗癌剂。伊马替尼是首创的苯氨基嘧啶衍生物激酶抑制剂，用于治疗慢性粒细胞白血病。使用混合方法，设计、合成了一系列含有苯基氨基嘧啶核的新型 5-苄叉-2-芳基亚氨基-4-噻唑烷酮衍生物，并测试了它们对 K562（慢性粒细胞白血病）、PC3（前列腺癌）和SHSY-5Y（神经母细胞瘤）细胞。由于在 K562 细胞上观察到了优异的抗癌活性，因此对 K562 细胞进行了所选化合物（8、15 和 34）的进一步生物学研究。为了合成设计的化合物，硫脲化合物在乙酸钠的存在下用 α-氯乙酸转化为 2-imino-1,3-thiazolidin-4-ones。5-Benzylidene-2-imino-1,3-thiazolidin-4-one 衍生物是通过 2-imino-1,3-thiazolidin-4-ones 与相关醛的 Knoevenagel 缩合获得的。评估了化合物 8、15 和 34 的细胞活力、细胞凋亡研究、细胞周期实验和 DNA 损伤分析。在 K562 细胞中，化合物 8、15 和 34 的 IC50 值分别为 5.26 ± 1.03、3.52 ± 0.91 和 8.16 ± 1.27 μM。优选地，与伊马替尼相比，这些化合物对L929细胞显示出较小的毒性。此外，化合物 8 和 15 以时间依赖性方式显着诱导早期和晚期细胞凋亡。化合物15和34在G0/G1期诱导细胞周期停滞，化合物8在G2/M期导致细胞周期停滞。基于 DNA 损伤分析，发现化合物 8 和 15 对 K562 细胞的基因毒性比伊马替尼更强。为了更深入地了解分子，通过分子对接研究预测了大多数活性化合物可能的 Abl 抑制机制。总之，本文报道了一系列新的 5-benzylidene-2-arylimino-4-thiazolidinone 衍生物及其有前景的抗癌活性。