The Synthesis of Glycyrrhetinic Acid Derivatives Containing A Nitrogen Heterocycle and Their Antiproliferative Effects in Human Leukemia Cells

被引：22

作者：

Gao, Yuan ^{[1
]}

Guo, Xin ^{[2
]}

Li, Xiaojing ^{[1
]}

Liu, Dan ^{[1
]}

Song, Dandan ^{[2
]}

Xu, Ye ^{[1
]}

Sun, Ming ^{[2
]}

Jing, Yongkui ^{[3
]}

Zhao, Linxiang ^{[1
]}

机构：

[1] Shenyang Pharmaceut Univ, Key Lab Struct Based Drugs Design & Discovery, Minist Educ, Shenyang 110016, Peoples R China

[2] Shenyang Pharmaceut Univ, Dept Pharmacol, Shenyang 110016, Peoples R China

[3] Mt Sinai Sch Med, New York, NY 10029 USA

来源：

MOLECULES | 2010年 / 15卷 / 06期

关键词：

antiproliferative; glycyrrhetinic acid derivative; leukemia; nitrogen heterocycle; NITRIC-OXIDE PRODUCTION; TRITERPENOIDS; INHIBITION;

D O I：

10.3390/molecules15064439

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Fifteen novel glycyrrhetinic acid derivatives containing a nitrogen heterocycle at C-30 and with different A-ring substituents were designed and synthesized. All of these derivatives have improved antiproliferative effects against human HL-60 leukemia cells. Compounds with a cyano-enone functionality on the A-ring exhibit greater growth inhibitory effects, compared to those with a 2-hydroxymethylene-3-keto, an isoxazole, or a 2-cyano-3-keto group. N-(2-cyano-3,11-dioxoolean-1,12-dien-30-yl)-4-piperidyl piperidine (9b) was found to be two-fold more potent than methyl 2-cyano-3,11-dioxooleana-1,12-dien-30-oate (CDODO-Me-11).

引用

收藏

页码：4439 / 4449

页数：11

相关论文

共 10 条

[1]

Structure-dependent inhibition of bladder and pancreatic cancer cell growth by 2-substituted glycyrrhetinic and ursolic acid derivatives [J].

Chadalapaka, Gayathri ;

Jutooru, Indira ;

McAlees, Alan ;

Stefanac, Tom ;

Safe, Stephen .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2008, 18 (08) :2633-2639

[2]

A novel dicyanotriterpenoid, 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-onitrile, active at picomolar concentrations for inhibition of nitric oxide production [J].

Honda, T ;

Honda, Y ;

Favaloro, FG ;

Gribble, GW ;

Suh, N ;

Place, AE ;

Rendi, MH ;

Sporn, MB .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (07) :1027-1030

[3]

Synthetic oleanane and ursane triterpenoids with modified rings A and C: A series of highly active inhibitors of nitric oxide production in mouse macrophages [J].

Honda, T ;

Rounds, BV ;

Bore, L ;

Finlay, HJ ;

Favaloro, FG ;

Suh, N ;

Wang, YP ;

Sporn, MB ;

Gribble, GW .

JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (22) :4233-4246

[4]

18β-glycyrrhetinic acid induces apoptotic cell death in SiHa cells and exhibits a synergistic effect against antibiotic anti-cancer drug toxicity [J].

Lee, Chung Soo ;

Kim, Yun Jeong ;

Lee, Min Sung ;

Han, Eun Sook ;

Lee, Sun Joo .

LIFE SCIENCES, 2008, 83 (13-14) :481-489

[5]

The synthetic triterpenoids CDDO-methyl ester and CDDO-ethyl amide prevent lung cancer induced by vinyl carbamate in A/J mice [J].

Liby, Karen ;

Royce, Darlene B. ;

Williams, Charlotte R. ;

Risingsong, Renee ;

Yore, Mark M. ;

Honda, Tadashi ;

Gribble, Gordon W. ;

Dmitrovsky, Ethan ;

Sporn, Thomas A. ;

Sporn, Michael B. .

CANCER RESEARCH, 2007, 67 (06) :2414-2419

[6]

The synthesis of 18β-glycyrrhetinic acid derivatives which have increased antiproliferative and apoptotic effects in leukemia cells [J].

Liu, Dan ;

Song, Dandan ;

Guo, Gang ;

Wang, Rui ;

Lv, Jinling ;

Jing, Yongkui ;

Zhao, Linxiang .

BIOORGANIC & MEDICINAL CHEMISTRY, 2007, 15 (16) :5432-5439

[7]

MURAMATSU Y, 2009, Patent No. 2009114132

[8]

ANTITUMOR-PROMOTING ACTIVITY OF GLYCYRRHETIC ACID IN MOUSE SKIN TUMOR-FORMATION INDUCED BY 7,12-DIMETHYLBENZ[A]ANTHRACENE PLUS TELEOCIDIN [J].

NISHINO, H ;

KITAGAWA, K ;

IWASHIMA, A .

CARCINOGENESIS, 1984, 5 (11) :1529-1530

[9]

Chemical modifications of natural triterpenes-glycyrrhetinic and boswellic acids: evaluation of their biological activity [J].

Rao, G. S. R. Subba ;

Kondaiah, Paturu ;

Singh, Sanjay K. ;

Ravanan, Palaniyandi ;

Sporn, Michael B. .

TETRAHEDRON, 2008, 64 (51) :11541-11548

[10]

Downregulation of c-FLIP, XIAP and Mcl-1 protein as well as depletion of reduced glutathione contribute to the apoptosis induction of glycyrrhetinic acid derivatives in leukemia cells [J].

Song, Dandan ;

Gao, Yuan ;

Wang, Rui ;

Liu, Dan ;

Zhao, Linxiang ;

Jing, Yongkui .

CANCER BIOLOGY & THERAPY, 2010, 9 (02) :96-108