Synthesis and Evaluation of Some New Aza-B-homocholestane Derivatives as Anticancer Agents

Marine Drugs

Bin Su¹  Aimin Zhou¹  Jianguo Cui²  Yanmin Huang²  Sijing Chen²  Chunfang Gan²  Qifu Lin²  Huacan Song³ 

[1] Clinical Chemistry Program, Department of Chemistry, SI 424, Cleveland State University, Cleveland, OH 44115, USA;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;

关键词: aza-B-homo-cholestane derivatives;    anticancer agents;    cytotoxicity;    3D multicellular spheroids screening;    apoptosis;   

DOI  :  10.3390/md12041715

来源: DOAJ

【 摘 要 】

Using analogues of some marine steroidal oximes as precursors, a series ofaza-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.

【 授权许可】

Unknown