Department of Chemistry, Guangxi Teachers Education University, Nanning 530001, China.
Steroids. 2011 Nov;76(12):1346-50. doi: 10.1016/j.steroids.2011.06.013. Epub 2011 Jul 13.
Using cholesterol as starting material, a series of 6-substituted-3-aza-A-homo-3-oxycholestanes and 6-substituted-4-aza-A-homo-3-oxycholestanes were synthesized by the oxidation, reduction, oximation, Beckman rearrangement and condensation reaction. These synthesized compounds displayed a distinct cytotoxicity against MGC 7901, HeLa and SMMC 7404 cancer cells. Our results revealed that the structures of functional groups at position-6 on the steroidal ring are crucial for the IC(50) value of antiproliferative activities of these compounds and the cytotoxic activity against MGC 7901 and SMMC 7404 cells was not significantly different between 4-N-lactams and 3-N-lactams when its 6-substituted group was a carbonyl or a hydroximino, but all 3-N-lactams showed a higher cytotoxicity against HeLa cells than 4-N-lactams. In particular, compounds 6, 8, 9 (IC(50)6: 6.5 μmol/L; 8: 7.7 μmol/L; 9: 5.6 μmol/L) were even more cytotoxic than cisplatin to HeLa cells (positive contrast, 10.1 μmol/L). The information obtained from the studies may be useful for the design of novel chemotherapeutic drugs.
以胆固醇为起始原料，通过氧化、还原、肟化、Beckman 重排和缩合反应，合成了一系列 6-取代-3-氮杂-A-同型-3-氧代胆甾烷和 6-取代-4-氮杂-A-同型-3-氧代胆甾烷。这些合成化合物对 MGC 7901、HeLa 和 SMMC 7404 癌细胞表现出明显的细胞毒性。我们的结果表明，甾体环上 6 位取代基的官能团结构对于这些化合物的增殖活性的 IC（50）值和对 MGC 7901 和 SMMC 7404 细胞的细胞毒性活性至关重要，当 6 位取代基为羰基或羟亚氨基时，4-N-内酰胺和 3-N-内酰胺之间的细胞毒性活性没有显著差异，但所有 3-N-内酰胺对 HeLa 细胞的细胞毒性均高于 4-N-内酰胺。特别是化合物 6、8、9（IC（50）：6.5 μmol/L；8：7.7 μmol/L；9：5.6 μmol/L）对 HeLa 细胞的细胞毒性甚至强于顺铂（阳性对照，10.1 μmol/L）。这些研究获得的信息可能有助于设计新型化疗药物。
