H.E.J. Research Institute of Chemistry, University of Karachi, Karachi 75270, Pakistan.
Steroids. 2011 Dec 20;76(14):1554-9. doi: 10.1016/j.steroids.2011.09.006. Epub 2011 Sep 22.
Pregnenolone (1) was used as a template to develop new anticancer compounds. Ring-D modification of 1 resulted in the synthesis of benzylidenes 2-17, pyrazolines 18-76, pyrazoles 85-91, hydrazones 77-84, and oximes 92-107 derivatives. The structure of compound 107 was also deduced through single crystal X-ray diffraction studies. The inclusion of furanyl and pyridyl rings to pregnenolone skeleton increases the cytotoxicity of all compounds significantly. Among benzylidene derivatives, only heterocyclic enone 8 (IC50=0.74 μM/mL against HepG2), and 17 (IC50=4.49 μM/mL against HepG2, IC50=5.01 μM/mL against MDA-MB-230 cancer cell line) exhibited a significant activity. The cytotoxicity data of pyrazoline derivatives 18-76 revealed that only furanyl bearing pyrazolines 40, 42-44, 48, and 49 exhibited significant activities. While all (O-carboxymethyl) oximes, hydazones, and pyrazoles derivatives of pregnenolone did not show any significant activity against both the cell lines. Thus the furanyl bearing enone 8 (IC50=0.74 μM/mL against HepG2), and its pyrazoline derivative 48 (IC50=0.91 μM/mL against MDA-MB-230 cancer cell lines) were identified as the most active compounds in all derivatives of pregnenolone.
孕烯醇酮（1）被用作开发新抗癌化合物的模板。1 的环-D 修饰导致合成了苯乙烯 2-17、吡唑啉 18-76、吡唑 85-91、腙 77-84 和肟 92-107 衍生物。化合物 107 的结构也通过单晶 X 射线衍射研究推断出来。将呋喃基和吡啶基引入孕烯醇酮骨架会显著提高所有化合物的细胞毒性。在苯乙烯衍生物中，只有杂环烯酮 8（对 HepG2 的 IC50=0.74 μM/mL）和 17（对 HepG2 的 IC50=4.49 μM/mL，对 MDA-MB-230 癌细胞系的 IC50=5.01 μM/mL）表现出显著的活性。吡唑啉衍生物 18-76 的细胞毒性数据表明，只有含有呋喃基的吡唑啉 40、42-44、48 和 49 表现出显著的活性。而孕烯醇酮的所有（O-羧甲基）肟、腙和吡唑衍生物对两种细胞系均无明显活性。因此，含呋喃基的烯酮 8（对 HepG2 的 IC50=0.74 μM/mL）及其吡唑啉衍生物 48（对 MDA-MB-230 癌细胞系的 IC50=0.91 μM/mL）被鉴定为孕烯醇酮所有衍生物中最活跃的化合物。
