新型齐墩果酸衍生物的合成及抗肿瘤活性  

Synthesis and anticancer activity of novel oleanolic acid derivatives

作　　者：丁晔[1] 张珍珍[2] 黄张建[1] 牟伊[1] 季晖[2] 赖宜生[1] 张奕华[1] 

机构地区：[1]中国药科大学新药研究中心,南京210009 [2]中国药科大学药理学教研室,南京210009

出　　处：《中国药科大学学报》2011年第5期385-391,共7页Journal of China Pharmaceutical University

基　　金：国家"重大新药创制"科技重大专项资助项目(No.2009ZX09103-090)~~

摘　　要：以齐墩果酸(OA)为先导化合物,经C28位羧基保护、C3位乙酰化、C12位氧化、C11位溴代后消除等7步连续反应合成了具有α,β-不饱和酮结构的OA衍生物;再以甘氨酸为连接基团,将不同取代的呋咱氮氧化物类一氧化氮供体与其偶联,获得新型OA衍生物,其结构经IR、MS及1H NMR确证。采用MTT法测定目标物和部分中间体对4种人肿瘤细胞的增殖抑制活性。结果表明,所有目标物的抗肿瘤活性均显著优于OA,其中10a-10e和10i对人肝癌HepG2细胞的增殖抑制活性与阳性对照药2-氰基-3,12-二氧代齐墩果烷-1,9(11)-二烯-28-羧酸甲酯(CDDO-Me)相当。Starting from oleanolic acid （OA）, the target compounds （10a-10i） were synthesized via introducting α,β-unsaturated ketone moiety to OA by 7-step successive reactions including benzylation, acetylation, oxidization, bromine substitution-elimination, etc. , followed by coupling of C28-carboxyl with substituted furoxans via a glycine linker. All the target compounds were identified by IR, MS and ^1H NMR. MTT assay results showed that compounds 11a-10i displayed much stronger inhibitory effects than OA on the proliferation of four human tumor cell lines. The anti-proliferative activity of 10a-10e and 10i against human hepatoma HepG2 cell was comparable to that of the positive control 2-cyano-3, 12-dioxooleana-1,9（11）-dien-28-oic acid methyl ester （CDDO-Me）.

关 键 词：齐墩果酸 α  β-不饱和酮 一氧化氮供体 呋咱氮氧化物 抗肿瘤活性 

分 类 号：R914.5[医药卫生—药物化学] R965[医药卫生—药学]