Synthesis and Evaluation of Some New Aza-B-homocholestane Derivatives as Anticancer Agents |
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| Authors: | Yanmin Huang Jianguo Cui Sijing Chen Qifu Lin Huacan Song Chunfang Gan Bin Su Aimin Zhou |
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| Institution: | 1.Key Laboratory of Beibu Gulf Environment Change and Resources Utilization, College of Chemistry and Life Science, Guangxi Teachers Education University, Nanning 530001, China; E-Mails: (Y.H.); (S.C.); (Q.L.); (C.G.);2.School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, China; E-Mail: ;3.Clinical Chemistry Program, Department of Chemistry, SI 424, Cleveland State University, Cleveland, OH 44115, USA; E-Mails: (B.S.); (A.Z.) |
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| Abstract: | 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. |
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| Keywords: | aza-B-homo-cholestane derivatives anticancer agents cytotoxicity 3D multicellular spheroids screening apoptosis |
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