甾体二芳基醚的合成及抗增殖活性。

Department of Organic Chemistry, University of Szeged, H-6720 Szeged, Hungary.

Institute of Pharmacodynamics and Biopharmacy, University of Szeged, H-6720 Szeged, Hungary.

Molecules. 2023 Jan 25;28(3):1196. doi: 10.3390/molecules28031196.

Novel 13α-estrone derivatives have been synthesized via direct arylation of the phenolic hydroxy function. Chan-Lam couplings of arylboronic acids with 13α-estrone as a nucleophilic partner were carried out under copper catalysis. The antiproliferative activities of the newly synthesized diaryl ethers against a panel of human cancer cell lines (A2780, MCF-7, MDA-MB 231, HeLa, SiHa) were investigated by means of MTT assays. The quinoline derivative displayed substantial antiproliferative activity against MCF-7 and HeLa cell lines with low micromolar IC values. Disturbance of tubulin polymerization has been confirmed by microplate-based photometric assay. Computational calculations reveal significant interactions of the quinoline derivative with the taxoid binding site of tubulin.

通过对酚羟基的直接芳基化，合成了新型 13α-雌酮衍生物。在铜催化作用下，用硼酸对芳基与 13α-雌酮作为亲核试剂进行 Chan-Lam 偶联。通过 MTT 法测定了新合成的二芳基醚对一系列人癌细胞系（A2780、MCF-7、MDA-MB 231、HeLa、SiHa）的增殖活性。喹啉衍生物对 MCF-7 和 HeLa 细胞系表现出显著的抗增殖活性，IC 值低至微摩尔。基于微孔板的光度测定法证实了微管聚合的干扰。计算计算揭示了喹啉衍生物与微管 taxoid 结合位点的显著相互作用。