University of Novi Sad, Faculty of Sciences, Department of Chemistry, Biochemistry and Environmental Protection, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia.
University of Novi Sad, Faculty of Sciences, Department of Chemistry, Biochemistry and Environmental Protection, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia.
Steroids. 2022 Dec;188:109118. doi: 10.1016/j.steroids.2022.109118. Epub 2022 Sep 29.
New steroidal D-homo androstane derivative, 5α,6β-dibromo-3β-hydroxy-17-oxa-17a-homoandrostan-16-one was synthesized and its structure was confirmed by NMR spectroscopy. In silico ADME properties of this compound were assessed using the SwissADME online prediction tool. Six human cancer cell lines (MDA-MB-231, MCF-7, PC3, HT-29, HeLa, and A549) and one human noncancerous cell line (MRC-5) were used for in vitro cytotoxicity testing. Novel steroidal dibromide was also tested for relative binding affinity for the ligand binding domain of estrogen receptor α and β or the androgen receptor using a published assay in yeast cells. Ligand binding domains of each steroid receptor were expressed in-frame with yellow fluorescent protein in yeast and the fluorescence intensity changes upon addition of test compound was measured. The new compound showed selective cytotoxic activity against HT-29 (colon adenocarcinoma) and A549 (lung adenocarcinoma) cell lines, as well as the potential to induce apoptosis in HT-29 cells, while results obtained from ligand binding assay in yeast suggested a lack of significant estrogenic or androgenic properties.
新的甾体 D-同型雄烷衍生物 5α,6β-二溴-3β-羟基-17-氧代-17α-同型雄烷-16-酮被合成，并通过 NMR 光谱确认其结构。使用 SwissADME 在线预测工具评估了该化合物的体内 ADME 性质。六种人癌细胞系（MDA-MB-231、MCF-7、PC3、HT-29、HeLa 和 A549）和一种人非癌细胞系（MRC-5）用于体外细胞毒性测试。新型甾体二溴化物还使用酵母细胞中发表的测定法，针对雌激素受体 α 和 β 或雄激素受体的配体结合域，测试了相对结合亲和力。每个甾体受体的配体结合域与黄色荧光蛋白在酵母中呈框架内表达，并测量加入测试化合物后荧光强度的变化。新化合物对 HT-29（结肠腺癌）和 A549（肺腺癌）细胞系表现出选择性细胞毒性活性，并且有可能诱导 HT-29 细胞凋亡，而酵母中配体结合测定的结果表明缺乏显著的雌激素或雄激素特性。
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