Center for Natural Product Research, Faculty of Chemistry, University of Havana, Zapata and G, Havana 10400, Cuba.
Laboratory of Synthetic and Biomolecular Chemistry, Faculty of Chemistry, University of Havana, Havana 10400, Cuba.
Int J Mol Sci. 2022 Aug 7;23(15):8775. doi: 10.3390/ijms23158775.
Colorectal cancer (CRC) is one of the most lethal cancers worldwide. If detected on time, surgery can expand life expectations of patients up to five more years. However, if metastasis has grown deliberately, the use of chemotherapy can play a crucial role in CRC control. Moreover, the lack of selectivity of current anticancer drugs, plus mutations that occur in cancerous cells, demands the development of new chemotherapeutic agents. Several steroids have shown their potentiality as anticancer agents, while some other compounds, such as Taxol and its derivatives bearing a carbamate functionality, have reached the market. In this article, the synthesis, characterization, and antiproliferative activity of four steroidal carbamates on mouse colon carcinoma CT26WT cells are described. Carbamate synthesis occurred via direct reaction between diosgenin, its B-ring modified derivative, and testosterone with phenyl isocyanate under a Brønsted acid catalysis. All obtained compounds were characterized by H and C Nuclear Magnetic Resonance (NMR), High Resolution Mass Spectroscopy (HRMS); their melting points are also reported. Results obtained from antiproliferative activity assays indicated that carbamates compounds have inhibitory effects on the growth of this colon cancer cell line. A molecular docking study carried out on Human Prostaglandin E Receptor (EP4) showed a high affinity between carbamates and protein, thus providing a valuable theoretical explanation of the in vitro results.
结直肠癌（CRC）是全球最致命的癌症之一。如果及时发现，手术可以将患者的预期寿命延长五年以上。然而，如果转移已经有意生长，化疗可以在 CRC 控制中发挥关键作用。此外，当前抗癌药物缺乏选择性，加上癌细胞发生的突变，需要开发新的化疗药物。一些甾体已显示出作为抗癌剂的潜力，而其他一些化合物，如紫杉醇及其带有氨基甲酸酯官能团的衍生物，已进入市场。在本文中，描述了四种甾体氨基甲酸酯在小鼠结肠癌细胞 CT26WT 上的合成、表征和抗增殖活性。氨基甲酸酯的合成是通过在布朗斯台德酸催化下，薯蓣皂苷元和其 B 环修饰的衍生物以及睾丸酮与苯异氰酸酯直接反应得到的。所有得到的化合物都通过 H 和 C 核磁共振（NMR）、高分辨率质谱（HRMS）进行了表征；还报告了它们的熔点。抗增殖活性测定的结果表明，氨基甲酸酯化合物对这种结肠癌细胞系的生长具有抑制作用。对人前列腺素 E 受体（EP4）进行的分子对接研究表明，氨基甲酸酯与蛋白质之间具有高亲和力，从而为体外结果提供了有价值的理论解释。
