Medicinal Chemistry Division, Indian Institute of Integrative Medicine, Jammu 180001, India.
Eur J Med Chem. 2013 May;63:279-89. doi: 10.1016/j.ejmech.2013.01.003. Epub 2013 Jan 11.
In the present study, novel spiro derivatives of α-santonin were prepared and tested for their anticancer activity against a panel of six human cancer cell lines. Spiro-isoxazoline and spiro-isoxazolidine derivatives have been generated on C-ring of α-santonin (α-methylene-γ-butyrolactone) by the 1,3-dipolar cycloaddition of α-santonin derivative 6 with nitrile oxides 7 and nitrones 9 respectively. Among all, compound 10b″ had shown IC50 of 0.01, 0.5 and 0.3 μM against PC-3, THP-1 and MCF-7 cell lines respectively. Further, flow cytometry studies showed that PC-3 cells treated with the spiro-isoxazolidine derivative 10b″ were arrested in the sub G1 phase of the cell cycle in a concentration dependent manner. The spiro-isoxazolidine derivative 10b″ also showed concentration dependent inhibitory activity against NF-κB, p65 with 57% inhibition in 24 h at 10 μM.
在本研究中，我们制备了新型 α-山道年螺环衍生物，并测试了它们对六种人癌细胞系的抗癌活性。通过α-山道年衍生物 6 与硝酮氧化物 7 和氮氧自由基 9 的 1,3-偶极环加成反应，在 C-环上生成了螺异噁唑啉和螺异噁唑烷衍生物。其中，化合物 10b″对 PC-3、THP-1 和 MCF-7 细胞系的 IC50 值分别为 0.01、0.5 和 0.3 μM。此外，流式细胞术研究表明，用螺异噁唑烷衍生物 10b″处理的 PC-3 细胞在细胞周期的亚 G1 期呈浓度依赖性阻滞。螺异噁唑烷衍生物 10b″对 NF-κB、p65 也具有浓度依赖性抑制活性，在 10 μM 时 24 小时内抑制率达到 57%。
