Center for Chemistry, Institute of Chemistry, Technology and Metallurgy, University of Belgrade, Studentski trg 12-16, P. O. Box 473, 11001 Belgrade, Serbia.
Institute of Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, Serbia.
Steroids. 2019 Aug;148:36-46. doi: 10.1016/j.steroids.2019.04.010. Epub 2019 May 8.
Eleven new steroidal mono- and bis(semicarbazones) 2a-e, 4d and 3a-e have been prepared starting from various 3-oxo-α,β-unsaturated steroids. Mono-semicarbazones 2a-e were further subjected to ethyl chloroacetate in boiling absolute ethanol but, instead of expected intramolecular cyclocondensation reaction products, the new carbazate esters 5a-e were obtained. The structures of all synthesized compounds and identification of each E/Z isomer were deduced by elemental analysis, HRMS, NMR, and IR spectroscopy. Preliminary screening for the cytotoxic activity in vitro of the new compounds has been conducted against three cancer cell lines, K562, Jurkat and HeLa cells. HeLa cells were the most sensitive while K562 cells were the least sensitive to the cytotoxic action of the novel steroid derivatives. Compounds 2e, 3c and 5e were found to have the best but still moderate cytotoxic effects. All tested compounds showed very weak antimicrobial activities. These results demonstrate that the replacement of thioxo group with carbonyl group in steroidal hydrazone derivatives resulted in decrease in their biological activity.
从各种 3-氧代-α，β-不饱和甾体开始，已经制备了 11 种新的甾体单和双（半卡巴腙）2a-e、4d 和 3a-e。单半卡巴腙 2a-e 进一步在沸腾的无水乙醇中用氯乙酸乙酯处理，但没有得到预期的分子内环缩合反应产物，而是得到了新的卡巴酯酯 5a-e。通过元素分析、高分辨率质谱、NMR 和 IR 光谱推导出所有合成化合物的结构，并确定了每个 E/Z 异构体的身份。对新化合物的体外细胞毒性活性进行了初步筛选，针对三种癌细胞系 K562、Jurkat 和 HeLa 细胞。HeLa 细胞对新型甾体衍生物的细胞毒性作用最敏感，而 K562 细胞最不敏感。化合物 2e、3c 和 5e 被发现具有最佳但仍然适度的细胞毒性作用。所有测试的化合物都表现出非常弱的抗菌活性。这些结果表明，在甾体腙衍生物中用羰基取代硫代基团会导致其生物活性降低。
