采用二苯脲和亚苄基乙酰肼之间的分子杂交设计了一系列新的靶向癌症的FGFR-1。设计的系列被合成并提交给 NCI-USA 筛选其对 NCI 癌细胞系的生长抑制活性。一些合成的杂交体对 NCI 癌细胞系表现出有希望的生长抑制活性，平均 GI% 介于 70.39% 和致死作用之间。进一步选择化合物 9a、9i、9j 和 9n-p 进行五剂量测定，所有测试的候选化合物均显示出有希望的抗增殖活性，GI50 达到亚微摩尔范围。一方面受9a对结肠癌的强大活性和众所周知的FGFR-1过表达的鼓舞，进一步选择其作为代表性实例来评估其对细胞周期的机制和HCT116细胞系的凋亡。有趣的是，9a被发现可以使HCT116细胞系的细胞周期暂停在G1期并诱导晚期细胞凋亡。同时，检查了所有合成的杂合体 9a-p 在 10 µM 浓度下抑制 FGFR-1 的潜力。发现化合物9a、9g、9h和9p具有有效的抑制活性，抑制百分比分别≥63.04%、58.31%、60.87%和79.84%。 FGFR-1 结合袋中 9a 的分子对接模拟证实了其能够实现 II 型 FGFR-1 抑制剂的特征性相互作用。通过 SwissADME 网络工具对 9a-p 的 ADME 特性的探索证明了其令人满意的理化特性，有助于发现新的抗癌药物。© 2024 Wiley periodicals LLC。

Molecular hybridization between diphenyl urea and benzylidene acetohydrazide was adopted for the design of a new series of FGFR-1 targeting cancer. The designed series was synthesized and submitted to NCI-USA to be screened for their growth inhibitory activity on NCI cancer cell lines. Some of the synthesized hybrids displayed promising growth inhibitory activity on NCI cancer cell lines with a mean GI% between 70.39% and a lethal effect. Compounds 9a, 9i, 9j, and 9n-p were further selected for a five-dose assay and all the tested candidates showed promising antiproliferative activity with GI50 reaching the submicromolar range. Encouraged by the potent activity of 9a on colon cancer on the one hand and the well-known overexpression of FGFR-1 in it on the other hand, it was further selected as a representative example to be evaluated for its mechanism on the cell cycle and apoptosis of HCT116 cell line. Interestingly, 9a was found to pause the cell cycle of the HCT116 cell line at the G1 phase and induced late apoptosis. In parallel, all the synthesized hybrids 9a-p were examined for their potential to inhibit FGFR-1 at 10 µM. Compounds 9a, 9g, 9h, and 9p were found to have potent inhibitory activity with % inhibition = 63.04%, 58.31%, 60.87% and 79.84%, respectively. Molecular docking simulation of 9a in the binding pocket of FGFR-1 confirms its capability to achieve the characteristic interactions of the type II FGFR-1 inhibitors. Exploration of the ADME properties of 9a-p by SwissADME web tool proved their satisfactory physicochemical properties for the discovery of new anticancer hits.© 2024 Wiley Periodicals LLC.