Synthetic and Biological Chemistry, Indian Institute of Integrative Medicine, Jammu 180001, India.
Eur J Med Chem. 2011 Aug;46(8):3210-7. doi: 10.1016/j.ejmech.2011.04.030. Epub 2011 Apr 29.
Several novel spiro derivatives of parthenin (1) have been synthesized by the dipolar cycloaddition using various dipoles viz; benzonitrile oxides, nitrones and azides with exocyclic double bond of C ring (α-methylene-γ-butyrolactone). Majority of the compounds exhibited improved anti-cancer activity compared to the parthenin, when screened for their in vitro cytotoxicity against three human cancer cell lines viz., SW-620, DU-145 and PC-3. In vivo screening of select analog revealed improved anti-cancer activity with low mammalian toxicity as compared to parthenin. The results of the cytotoxicity pattern of these derivatives reveals the SAR of these sesquiterpinoid lactones and possible role of α,β-unsaturated ketone of parthenin in inhibiting NF-kB. A mechanistic correlation of anti-cancer activity along with in vivo and western blotting experiments has been described.
几种新型的苦皮藤素（1）螺环衍生物已通过各种偶极子（如苯甲腈氧化物、氮氧化物和叠氮化物）与 C 环（α-亚甲基-γ-丁内酯）的环外双键的偶极环加成反应合成。与苦皮藤素相比，当对三种人类癌细胞系（SW-620、DU-145 和 PC-3）进行体外细胞毒性筛选时，大多数化合物表现出更好的抗癌活性。与苦皮藤素相比，对选择的类似物进行体内筛选显示出更好的抗癌活性和低的哺乳动物毒性。这些衍生物的细胞毒性模式的结果揭示了这些倍半萜内酯的 SAR 和苦皮藤素中α，β-不饱和酮在抑制 NF-kB 中的可能作用。已经描述了抗癌活性的机制相关性以及体内和 Western 印迹实验。
