Zhou Dai-Ying, Zhang Kun, Conney Allan H, Ding Ning, Cui Xiao-Xing, Wang Hui, Verano Michael, Zhao Su-Qing, Fan Yan-Xiong, Zheng Xi, Du Zhi-Yun
Allan H Conney Laboratory for Research, Institute of Natural Medicinal Chemistry & Green Chemistry, Guangdong University of Technology.
Chem Pharm Bull (Tokyo). 2013;61(11):1149-55. doi: 10.1248/cpb.c13-00507. Epub 2013 Aug 27.
Eleven curcumin-related compounds containing a benzyl piperidone moiety were synthesized and evaluated for their effects on cultured prostate cancer PC-3 cells, pancreas cancer BxPC-3 cells, colon cancer HT-29 cells and lung cancer H1299 cells. Inhibitory effects of these compounds on the growth of PC-3, BxPC-3, HT-29 and H1299 cells were determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and trypan blue exclusion assay. Compounds benzyl piperidone 2 (P2), P4, P7, 4-bromo-2-fluoro-benzyl piperidone 2 (PFBr2), PFBr3 and PFBr4 (see syntheses and structures in Figs. 1, 2) exhibited potent inhibitory effects on the growth of cultured PC-3, BxPC-3, HT-29 and H1299 cells. The IC50 for these compounds was lower than 2 µM in all four cell lines. PFBr4 was 41-, 36-, 40- and 46-fold more active than curcumin for inhibiting the growth of PC-3, BxPC-3, HT-29 and H1299 cells, respectively. The benzyl piperidone-containing compounds studied also stimulated apoptosis in PC-3 cells. Mechanistic studies indicate that the effects of both curcumin and PFBr4 on PC-3 cells were associated with a decrease in phospho-Akt and phospho-extracellular signal-regulated kinase (Erk)1/2. The present study indicates that P2, P4, P7, PFBr2, PFBr3 and PFBr4 may have useful effects on human cancer cells.
合成了11种含有苄基哌啶酮部分的姜黄素相关化合物，并评估了它们对培养的前列腺癌PC-3细胞、胰腺癌BxPC-3细胞、结肠癌HT-29细胞和肺癌H1299细胞的作用。通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)法和台盼蓝排斥试验测定这些化合物对PC-3、BxPC-3、HT-29和H1299细胞生长的抑制作用。化合物苄基哌啶酮2(P2)、P4、P7、4-溴-2-氟苄基哌啶酮2(PFBr2)、PFBr3和PFBr4(见图1、2中的合成方法和结构)对培养的PC-3、BxPC-3、HT-29和H1299细胞的生长表现出强效抑制作用。在所有四种细胞系中，这些化合物的半数抑制浓度(IC50)均低于2μM。PFBr4在抑制PC-3、BxPC-3、HT-29和H1299细胞生长方面分别比姜黄素活性高41倍、36倍、40倍和46倍。所研究的含苄基哌啶酮的化合物还能诱导PC-3细胞凋亡。机制研究表明，姜黄素和PFBr4对PC-3细胞的作用均与磷酸化Akt和磷酸化细胞外信号调节激酶(Erk)1/2的减少有关。本研究表明，P2、P4、P7、PFBr2、PFBr3和PFBr4可能对人类癌细胞有有益作用。
