Ferrari Erika, Lazzari Sandra, Marverti Gaetano, Pignedoli Francesca, Spagnolo Ferdinando, Saladini Monica
Department of Chemistry, University of Modena and Reggio Emilia, Via Campi 183, 41100 Modena, Italy.
Bioorg Med Chem. 2009 Apr 15;17(8):3043-52. doi: 10.1016/j.bmc.2009.03.016. Epub 2009 Mar 14.
New curcumin derivatives are synthesized in order to improve chemical properties of curcumin. The aromatic ring glycosylation of curcumin provides more water-soluble compounds with a greater kinetic stability which is a fundamental feature for drug bioavailability. The glycosylation reaction is quite simple, low cost, with high yield and minimum waste. NMR data show that the ability of curcumin to coordinate metal ion, in particular Ga(III), is maintained in the synthesized products. Although the binding of glucose to curcumin reduces the cytotoxicity of the derivatives towards cisplatin (cDDP)-sensitive and -resistant human ovarian carcinoma cell lines, the compounds display a good selectivity since they are much less toxic against non-tumourigenic Vero cells. The combination of cDDP with the most active glycosyl-curcuminoid drug against both cDDP-sensitive and -resistant as well as against Vero cell lines is tested. The results show an improvement of cDDP efficacy with higher selectivity towards cancer cells than non-cancer cells. These studies indicate the need for developing new valid components of drug treatment protocols to cDDP-resistant cells as well.
为改善姜黄素的化学性质，合成了新的姜黄素衍生物。姜黄素的芳香环糖基化提供了更多具有更高动力学稳定性的水溶性化合物，这是药物生物利用度的一个基本特征。糖基化反应相当简单、成本低、产率高且废物最少。核磁共振数据表明，合成产物中保留了姜黄素与金属离子（特别是Ga(III)）配位的能力。虽然葡萄糖与姜黄素的结合降低了衍生物对顺铂（cDDP）敏感和耐药的人卵巢癌细胞系的细胞毒性，但这些化合物具有良好的选择性，因为它们对非致瘤性Vero细胞的毒性要小得多。测试了cDDP与对cDDP敏感和耐药以及对Vero细胞系最具活性的糖基姜黄素类药物的组合。结果表明，cDDP的疗效有所提高，对癌细胞的选择性高于对非癌细胞的选择性。这些研究表明，也需要开发针对cDDP耐药细胞的新的有效药物治疗方案成分。
