Gil-Edo Raquel, Royo Santiago, Carda Miguel, Falomir Eva
Inorganic and Organic Chemistry Department, University Jaume I, 12071 Castellón, Spain.
Institute of Agronomic Engineering for Development, Polytechnic University of Valencia, 46022 Valencia, Spain.
Pharmaceuticals (Basel). 2023 May 29;16(6):808. doi: 10.3390/ph16060808.
This work focuses on the development of thirteen benzylethylenearyl ureas and one carbamate. After the synthesis and purification of the compounds, we studied their antiproliferative action on cell lines, such as HEK-293, and cancer ones, such as HT-29, MCF-7 or A-549, on the immune Jurkat T-cells and endothelial cells HMEC-1. Compounds , , and were selected for further biological studies to establish their potential as immunomodulating agents. Some of the derivatives exhibited significant inhibitory effects on both targets: PD-L1 and VEGFR-2 in the HT-29 cell line, showing that urea is active against both targets. Some compounds could inhibit more than 50% of cancer cell proliferation compared to non-treated ones when assessed in co-cultures using HT-29 and THP-1 cells. In addition, they significantly reduced CD11b expression, which is a promising target for immune modulation in anticancer immunotherapies.
这项工作聚焦于13种苄基乙烯基芳基脲和1种氨基甲酸酯的开发。在化合物合成与纯化后，我们研究了它们对细胞系（如HEK - 293）、癌细胞系（如HT - 29、MCF - 7或A - 549）、免疫Jurkat T细胞以及内皮细胞HMEC - 1的抗增殖作用。选择化合物 、 、 和 进行进一步的生物学研究，以确定它们作为免疫调节药物的潜力。一些衍生物对两个靶点均表现出显著抑制作用：HT - 29细胞系中的PD - L1和VEGFR - 2，表明脲 对这两个靶点均有活性。在使用HT - 29和THP - 1细胞进行共培养评估时，与未处理的细胞相比，一些化合物可抑制超过50%的癌细胞增殖。此外，它们显著降低了CD11b的表达，这是抗癌免疫疗法中免疫调节的一个有前景的靶点。
