Synthesis of fluorescent derivatives of wortmannin and demethoxyviridin as probes for phosphatidylinositol 3-kinase

被引：11

作者：

Giner, JL ^{[1
]}

Kehbein, KA

Cook, JA

Smith, MC

Vlahos, CJ

Badwey, JA

机构：

[1] SUNY Coll Environm Sci & Forestry, Dept Chem, Syracuse, NY 13210 USA

[2] Lilly Res Labs, Indianapolis, IN 46285 USA

[3] Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Ctr Expt Therapeut & Reperfus Injury, Boston, MA 02115 USA

[4] Harvard Univ, Sch Med, Boston, MA 02115 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 09期

基金：

美国国家科学基金会;

关键词：

enzyme inhibitors; fluorescent probes; phosphoinositol; 3-kinase; steroidal drugs;

D O I：

10.1016/j.bmcl.2006.01.091

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Fluorescent analogs were synthesized of the potent PI 3-kinase inhibitors, wortmannin and demethoxyviridin. The esterification of 11-deacetylwortmannin, 17-hydroxywortmannin, and demethoxyviridin with the fluorescent carboxylic acids NBD-sarcosine and 7-dimethylaminocoumarin-4-acetic acid generated six novel fluorescent esters. Potent inhibition of PI 3-kinase-alpha was observed for the derivatives of 11-desacetylwortmannin and demethoxyviridin. (C) 2006 Elsevier Ltd. All rights reserved.

引用

页码：2518 / 2521

页数：4

共 24 条

[1] DEMETHOXYVIRIDIN AND DEMETHOXYVIRIDIOL - NEW FUNGAL METABOLITES [J].

ALDRIDGE, DC ;

TURNER, WB ;

GEDDES, AJ ;

SHELDRICK, B .

JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1975, (10) :943-945

[2] WORTMANNIN IS A POTENT PHOSPHATIDYLINOSITOL 3-KINASE INHIBITOR - THE ROLE OF PHOSPHATIDYLINOSITOL 3,4,5-TRISPHOSPHATE IN NEUTROPHIL RESPONSES [J].

ARCARO, A ;

WYMANN, MP .

BIOCHEMICAL JOURNAL, 1993, 296 :297-301

[3] SYNTHESIS AND CHARACTERIZATION OF 7-NITROBENZO-2-OXA-1,3-DIAZOLE (NBD)-LABELED FLUORESCENT OPIOIDS [J].

ARCHER, S ;

MEDZIHRADSKY, F ;

SEYEDMOZAFFARI, A ;

EMMERSON, PJ .

BIOCHEMICAL PHARMACOLOGY, 1992, 43 (02) :301-306

[4] INHIBITION OF THE PHAGOCYTOSIS-INDUCED RESPIRATORY BURST BY THE FUNGAL METABOLITE WORTMANNIN AND SOME ANALOGS [J].

BAGGIOLINI, M ;

DEWALD, B ;

SCHNYDER, J ;

RUCH, W ;

COOPER, PH ;

PAYNE, TG .

EXPERIMENTAL CELL RESEARCH, 1987, 169 (02) :408-418

[5]

COOK J, UNPUB

[6] Synthesis and in vitro evaluation of new wortmannin esters: Potent inhibitors of phosphatidylinositol 3-kinase [J].

Creemer, LC ;

Kirst, HA ;

Vlahos, CJ ;

Schultz, RM .

JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (25) :5021-5024

[7] WORTMANNIN AND 1-BUTANOL BLOCK ACTIVATION OF A NOVEL FAMILY OF PROTEIN-KINASES IN NEUTROPHILS [J].

DING, JB ;

BADWEY, JA .

FEBS LETTERS, 1994, 348 (02) :149-152

[8] ANTAGONISTS OF PHOSPHATIDYLINOSITOL 3-KINASE BLOCK ACTIVATION OF SEVERAL NOVEL PROTEIN-KINASES IN NEUTROPHILS [J].

DING, JB ;

VLAHOS, CJ ;

LIU, RC ;

BROWN, RF ;

BADWEY, JA .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (19) :11684-11691

[9] SELECTIVE FUNCTIONALIZATION OF WORTMANNIN USING FURAN RING MASKING [J].

HAEFLIGER, W ;

KIS, Z ;

HAUSER, D .

HELVETICA CHIMICA ACTA, 1975, 58 (06) :1620-1628

[10]

Haugland R.P., 1996, Handbook of Fluorescent Probes and Research Chemicals

← 1 2 3 →