Huang Yanmin, Cui Jianguo, Chen Sijing, Lin Qifu, Song Huacan, Gan Chunfang, Su Bin, Zhou Aimin
Key Laboratory of Beibu Gulf Environment Change and Resources Utilization, College of Chemistry and Life Science, Guangxi Teachers Education University, Nanning 530001, China.
School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, China.
Mar Drugs. 2014 Mar 25;12(4):1715-31. doi: 10.3390/md12041715.
Using analogues of some marine steroidal oximes as precursors, a series of aza-B-homocholestane derivatives possessing different substituted groups at the 3-position of the steroidal nucleus were synthesized. Their biological activity against cancer cell proliferation was determined with multiple cancer cell lines. Aza-B-homocholestane derivatives possessing 3-hydroxyl, 3-hydroximino and 3-thiosemicarbazone groups displayed remarkable cytotoxicity to cancer cells via apoptosis inducing mechanism. Compounds 5, 10, 12, 15 and 18 exhibited better potency to inhibit cancer cell proliferation. In addition, compound 15 was further evaluated with three dimensional (3D) multicellular spheroids assay to determine its potency against spheroid growth. The structure-activity relationship (SAR) generated in the studies is valuable for the design of novel chemotherapeutic agents.
以一些海洋甾体肟类似物为前体，合成了一系列在甾体核3位具有不同取代基的氮杂-β-高胆甾烷衍生物。用多种癌细胞系测定了它们对癌细胞增殖的生物活性。具有3-羟基、3-羟亚氨基和3-硫代半卡巴腙基团的氮杂-β-高胆甾烷衍生物通过诱导凋亡机制对癌细胞表现出显著的细胞毒性。化合物5、10、12、15和18表现出更好的抑制癌细胞增殖的能力。此外，化合物15通过三维（3D）多细胞球体试验进一步评估，以确定其对球体生长的抑制能力。该研究中产生的构效关系（SAR）对于新型化疗药物的设计具有重要价值。
