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

共 22 条

[1] Studies of the potential genotoxic effects of furoxans: The case of CAS 1609 and of the water-soluble analogue of CHF 2363
Balbo, S.
Lazzarato, L.
Di Stilo, A.
Fruttero, R.
Lombaert, N.
Kirsch-Volders, M.
[J]. TOXICOLOGY LETTERS, 2008, 178 (01) : 44 - 51
[2] Propylene Glycol-Linked Amino Acid/Dipeptide Diester Prodrugs of Oleanolic Acid for PepT1-Mediated Transport: Synthesis, Intestinal Permeability, and Pharmacokinetics
Cao, Feng
Gao, Yahan
Wang, Meng
Fang, Lei
Ping, Qineng
[J]. MOLECULAR PHARMACEUTICS, 2013, 10 (04) : 1378 - 1387
[3] Ethylene Glycol-Linked Amino Acid Diester Prodrugs of Oleanolic Acid for PepT1-Mediated Transport: Synthesis, Intestinal Permeability and Pharmacokinetics
Cao, Feng
Jia, Jinghao
Yin, Zhi
Gao, Yahan
Sha, Lei
Lai, Yisheng
Ping, Qineng
Zhang, Yihua
[J]. MOLECULAR PHARMACEUTICS, 2012, 9 (08) : 2127 - 2135
[4] Nitric oxide release: Part II. Therapeutic applications
Carpenter, Alexis W.
Schoenfisch, Mark H.
[J]. CHEMICAL SOCIETY REVIEWS, 2012, 41 (10) : 3742 - 3752
[5] Design, synthesis, and antihepatocellular carcinoma activity of nitric oxide releasing derivatives of oleanolic acid
Chen, Li
Zhang, Yihua
Kong, Xiangwen
Lan, Edward
Huang, Zhangjian
Peng, Sixun
Kaufman, Daniel L.
Tian, Jide
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 2008, 51 (15) : 4834 - 4838
[6] RT-PCR analysis of ABC, SLC and SLCO drug transporters in human lung epithelial cell models
Endter, Sibylle
Francombe, Danielle
Ehrhardt, Carsten
Gumbleton, Mark
[J]. JOURNAL OF PHARMACY AND PHARMACOLOGY, 2009, 61 (05) : 583 - 591
[7] 5′-amino acid esters of antiviral nucleosides, acyclovir, and AZT are absorbed by the intestinal PEPT1 peptide transporter
Han, HK
de Vrueh, RLA
Rhie, JK
Covitz, KMY
Smith, PL
Lee, CP
Oh, DM
Sadee, W
Amidon, GL
[J]. PHARMACEUTICAL RESEARCH, 1998, 15 (08) : 1154 - 1159
[8] Synthesis and anti-human hepatocellular carcinoma activity of new nitric oxide-releasing glycosyl derivatives of oleanolic acid
Huang, Zhangjian
Zhang, Yihua
Zhao, Li
Jing, Yongwang
Lai, Yisheng
Zhang, Luyong
Guo, Qinglong
Yuan, Shengtao
Zhang, Jianjun
Chen, Li
Peng, Sixun
Tian, Jide
[J]. ORGANIC & BIOMOLECULAR CHEMISTRY, 2010, 8 (03) : 632 - 639
[9] Dose-linear pharmacokinetics of oleanolic acid after intravenous and oral administration in rats
Jeong, Dong Won
Kim, Young Hoon
Kim, Hui Hyun
Ji, Hye Young
Yoo, Sun Dong
Choi, Won Rack
Lee, Soo Min
Han, Chang-Kyun
Lee, Hye Suk
[J]. BIOPHARMACEUTICS & DRUG DISPOSITION, 2007, 28 (02) : 51 - 57
[10] NOSH-Aspirin: A Novel Nitric Oxide-Hydrogen Sulfide-Releasing Hybrid: A New Class of Anti-inflammatory Pharmaceuticals
Kodela, Ravinder
Chattopadhyay, Mitali
Kashfi, Khosrow
[J]. ACS MEDICINAL CHEMISTRY LETTERS, 2012, 3 (03): : 257 - 262

← 1 2 3 →