17-[3,6-二氧杂-8-N-（取代肉桂酰基）辛二胺]-17-去甲氧基格尔德霉素新颖衍生物的合成

Twenty six new 17-[3,6-dioxa-8-N-(substituted cinnamyol)octanediamino]-17-demethoxygeldanamycins were designed, synthesized and evaluated for their cytotoxicities against the growth of human breast cancer cell line MDA-MB-231 and binding affinities to heat shock protein 90 (Hsp90). Among these derivatives, 17-(3,6-dioxa-8-N-((E)-3-(3,5-dimethoxyphenyl)acrylamido)octanediamino)-17-demethoxygeldanamycin (3u), was identified as the most potent one (IC50 = 1.5 junol/L, K-d = 1.14 mu mol/L). Additionally, influence of substitutions at the cinnamyol group on the bioactivities of this type of Geldanamycin (GA) derivatives was discussed. This study was anticipated to provide reference for the further structure modifications of GA for developing antitumor agents.