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

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.

Synthesis, characterization and in vitro cytotoxic activities of new steroidal thiosemicarbazones and thiadiazolines

“…2). [44][45][46][47][48][49] In a similar way, another goal of this work was to perform an extensive investigation of the in vitro cytotoxic activity of the newly synthesized steroid derivatives. These compounds were tested against six human malignant cell lines: cervical adenocarcinoma (HeLa), two breast cancer cell lines (MDA-MB-453 and MDA-MB-361), chronic myelogenous leukemia (K562), colon adenocarcinoma (LS174) and lung adenocarcinoma (A549) cells.…”

The Structural Diversity and Biological Activity of Steroid Oximes

“…Using analogs of compounds 4i and 4j as precursors, Huang et al designed and synthesized novel steroidal oximes and then evaluated their anticancer efficacy against a panel of six cancer cell lines [ 76 ]. Of all the synthesized compounds, oxime 4aw ( Figure 7 ) was the most powerful oxime, especially in HeLa and GNE2 cancer cell lines with IC 50 values of 9.1 and 11.3 µM, respectively ( Table 6 ).…”

Recent Advance of Synthesis and Bioactivities for Steroids with Special Steroidal Nucleus

“…[47,48] , 去进一步增强甾体化合物在某个方面的生物活性. 我们 分 别 对 某 些 A-homo [49,50] , B-homo [51] , C-homo [52] 及 D-homo [53] 类型的甾体扩环内酰胺化合物及 B-homo [54] 类型甾体扩环内酯化合物进行了合成及抗肿瘤活性研 究, 结果表明具有胆甾烷支链结构的化合物均具有较好 的抑制肿瘤细胞生长增殖活性, 对肿瘤细胞的抑制作用 主要通过诱导细胞凋亡的方式, 某些 A-nomo 及 B-homo 内酰胺化合物在动物模型中对移植肿瘤也表现出一定 的抑制作用. 由此可见, 对于具有特殊甾核结构甾体化 合物的研究来说, 保持胆甾烷类型的 17-支链结构, 然 后对甾核结构进行不同的改造或修饰, 可期望获得具有 更好抗肿瘤活性的此类化合物.…”