Inorganic and Organic Chemistry Department, Universidad Jaume I, 12071 Castellón, Spain.
Physical and Analytical Chemistry Department. Universidad Jaume I, 12071 Castellón, Spain.
Int J Mol Sci. 2022 Jun 24;23(13):7049. doi: 10.3390/ijms23137049.
Twenty-six triazole-based derivatives were designed for targeting both PD-L1 (programmed death receptor ligand 1) and VEGFR-2 (vascular endothelial growth factor receptor 2). These compounds were synthetized and biologically evaluated as multitarget inhibitors of VEGFR-2, PD-L1 and c-Myc proteins. The antiproliferative activity of these molecules on several tumor cell lines (HT-29, A-549, and MCF-7) and on the non-tumor cell line HEK-293 was determined. The effects on the abovementioned biological targets were evaluated for some selected compounds. Compound , bearing a -chlorophenyl group, showed better results than sorafenib in regard to the downregulation of VEGFR-2 and a similar effect to BMS-8 on both PD-L1 and c-Myc proteins. The antiangiogenic and antivascular activities of chloro derivatives were also established by endothelial microtube formation assay on Matrigel.
设计了 26 种三唑类衍生物，以同时靶向 PD-L1（程序性死亡受体配体 1）和 VEGFR-2（血管内皮生长因子受体 2）。这些化合物被合成并作为 VEGFR-2、PD-L1 和 c-Myc 蛋白的多靶点抑制剂进行了生物学评估。这些分子对几种肿瘤细胞系（HT-29、A-549 和 MCF-7）和非肿瘤细胞系 HEK-293 的增殖活性进行了测定。对一些选定的化合物评估了对上述生物靶标的影响。带有 -氯苯基的化合物在下调 VEGFR-2 方面比索拉非尼表现更好，对 PD-L1 和 c-Myc 蛋白的作用与 BMS-8 相似。氯衍生物的抗血管生成和抗血管活性也通过在 Matrigel 上的内皮小管形成测定得到了证实。
