Combination of Amino Acid/Dipeptide with Nitric Oxide Donating Oleanolic Acid Derivatives as PepT1 Targeting Antitumor Prodrugs

被引：55

作者：

Fang, Lei ^{[1
,2
,3
]}

Wang, Meng ^{[3
]}

Gou, Shaohua ^{[1
,2
]}

Liu, Xuying ^{[1
,2
]}

Zhang, Huan ^{[1
,2
,3
]}

Cao, Feng ^{[3
]}

机构：

[1] Southeast Univ, Sch Chem & Chem Engn, Pharmaceut Res Ctr, Nanjing 211189, Jiangsu, Peoples R China

[2] Southeast Univ, Sch Chem & Chem Engn, Jiangsu Prov Hitech Key Lab Biomed Res, Nanjing 211189, Jiangsu, Peoples R China

[3] China Pharmaceut Univ, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2014年 / 57卷 / 03期

基金：

中国国家自然科学基金;

关键词：

TRITERPENOIDS; TRANSPORTERS;

D O I：

10.1021/jm401634d

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

By taking advantage of the cytotoxic effect of nitric oxide (NO) and PepT1 for molecule-targeted drug delivery, a series of amino acid/dipeptide diester prodrugs of NO-donating oleanolic acid derivatives were designed and synthesized. Two prodrugs 6a and 8a showed potent cytotoxcity, which is probably due to their high PepT1 affinity and NO-releasing ability. Furthermore, the aqueous solubility of the prodrugs was also significantly enhanced because of the hydrophilic amino acid/dipeptide promoiety.

引用

页码：1116 / 1120

页数：5