Abstract

New steroidal D-homo androstane derivatives with 5β,6β-epoxy-3,16-dicarbonyl, 6α- and 6β-hydroxy-3,16-dicarbonyl and 3β,5α-dihydroxy-6,16-dicarbonyl moieties were synthesized and confirmed by NMR spectroscopy. Novel and starting compounds were evaluated for their potential cytotoxicity in vitro against seven human cancer cell lines (MCF-7, MDA-MB-231, PC3, HeLa, HT-29, A549 and CEM) and one human noncancerous cell line (MRC-5). The most sensitive cell line was MDA-MB-231 derived from female reproductive tissue, wherein all compounds showed moderate to strong cytotoxic activity. Also, new compound with 5β,6β-epoxy-3,16-dicarbonyl moieties showed strong cytotoxic activity against colon adenocarcinoma (HT-29). In this work, in silico ADME properties of novel compounds were assessed by comparing calculated molecular properties with Lipinski, Veber, Egan, Ghose and Muegge criteria.

Graphic abstract

The synthesis and structure elucidation of new oxygen-containing androstane derivatives was reported. New derivatives were tested for their in silico ADME properties and cytotoxicity against different human cancer cell lines.

中文翻译：

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新的含氧雄烷衍生物：合成和生物潜力

摘要

合成了具有5β，6β-环氧-3,16-二羰基，6α-和6β-羟基-3,16-二羰基和3β，5α-二羟基-6,16-二羰基的甾族D-高雄甾烷衍生物。 NMR光谱。评估了新型和起始化合物在体外对七种人类癌细胞系（MCF-7，MDA-MB-231，PC3，HeLa，HT-29，A549和CEM）和一种人类非癌细胞系（MRC- 5）。最敏感的细胞系是源自雌性生殖组织的MDA-MB-231，其中所有化合物均显示出中度至强细胞毒活性。而且，具有5β，6β-环氧-3，16-二羰基部分的新化合物显示出对结肠腺癌（HT-29）的强细胞毒性活性。在这项工作中，计算机 通过将计算的分子特性与Lipinski，Veber，Egan，Ghose和Muegge标准进行比较，评估了新化合物的ADME特性。

图形摘要

报道了新的含氧雄烷衍生物的合成和结构解析。测试了新衍生物的计算机模拟ADME特性以及对不同人类癌细胞系的细胞毒性。