Synthesis of novel ursolic acid heterocyclic derivatives with improved abilities of antiproliferation and induction of p53, p21waf1 and NOXA in pancreatic cancer cells

被引：59

作者：

Leal, Ana S. ^{[1
,2
,3
]}

Wang, Rui ^{[3
]}

Salvador, Jorge A. R. ^{[1
,2
]}

Jing, Yongkui ^{[3
]}

机构：

[1] Univ Coimbra, Quim Farmaceut Lab, Fac Farm, P-3000548 Coimbra, Portugal

[2] Univ Coimbra, CNC Ctr Neurociencias & Biol Celular, P-3000517 Coimbra, Portugal

[3] Mt Sinai Sch Med, Tisch Canc Inst, Div Hematol Oncol, New York, NY 10029 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2012年 / 20卷 / 19期

关键词：

Ursolic acid; Heterocyclic derivatives; Antiproliferative; p53; NOXA; OLEANOLIC ACID; INHIBITION; APOPTOSIS; PROLIFERATION; ACTIVATION; PATHWAY; GROWTH;

D O I：

10.1016/j.bmc.2012.08.010

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A series of new heterocyclic derivatives of ursolic acid 1 were synthesized and evaluated for their anti-proliferative activity against AsPC-1 pancreatic cancer cells. Compounds 24-32, with an alpha,beta unsaturated ketone in conjugation with an heterocyclic ring in ring A have improved antiproliferative activities. Compound 32 is the most active compound with an IC50 of 1.9 mu M which is sevenfold more active than ursolic acid 1. Compound 32 arrests cell cycle in G1 phase and induces apoptosis in AsPC-1 cells with upregulation of p53, p21(waf1) and NOXA protein levels. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：5774 / 5786

页数：13

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