A novel type of nonsteroidal estrone sulfatase inhibitors

被引：29

作者：

Jütten, P ^{[1
]}

Schumann, W ^{[1
]}

Härtl, A ^{[1
]}

Heinisch, L ^{[1
]}

Gräfe, U ^{[1
]}

Werner, W ^{[1
]}

Ulbricht, H ^{[1
]}

机构：

[1] Hans Knoll Inst Nat Prod Res, D-07745 Jena, Germany

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2002年 / 12卷 / 10期

关键词：

D O I：

10.1016/S0960-894X(02)00171-3

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Madurahydroxylactone (MHL) is a secondary metabolite produced by the soil bacterium Nonomuria rubra and belongs to the family of benzo[a]naphthacenequinones. We report the initial results and structure-activity relationships of our study into a series of thiosemicarbazone derivatives of madurahydroxylactone as potential nonsteroidal inhibitors of the enzyme estrone sulfatase. The most active compound. the cyclohexylthiosemicarbazone, was shown to be a non-competitive inhibitor with a K-i of 0.35 muM. This compound is devoid of estrogenic properties and showed low acute toxicity in the hen's fertile egg screening test. (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

收藏

页码：1339 / 1342

页数：4

相关论文

共 18 条

[1] Novel inhibitors of the enzyme estrone sulfatase (ES) [J].

Ahmed, S ;

James, K ;

Owen, CP ;

Patel, CK ;

Patel, M .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2001, 11 (06) :841-844

[2] Stimulation of MCF-7 breast cancer cell proliferation by estrone sulfate and dehydroepiandrosterone sulfate: inhibition by novel non-steroidal steroid sulfatase inhibitors [J].

Billich, A ;

Nussbaumer, P ;

Lehr, P .

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 2000, 73 (05) :225-235

[3] Synthesis and sulfatase inhibitory activities of (E)- and (Z)-4-hydroxytamoxifen sulfamates [J].

Chu, GH ;

Peters, A ;

Selcer, KW ;

Li, PK .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1999, 9 (02) :141-144

[4]

ELGER WS, 1995, J STEROID BIOCHEM, V66, P395

[5] FERMENTATION, ISOLATION, AND BIOLOGICAL-ACTIVITY OF MADURAMYCIN - NEW ANTIBIOTIC FROM ACTINOMADURA-RUBRA [J].

FLECK, WF ;

STRAUSS, DG ;

MEYER, J ;

PORSTENDORFER, G .

ZEITSCHRIFT FUR ALLGEMEINE MIKROBIOLOGIE, 1978, 18 (06) :389-398

[6]

HAGEMANN H, 1983, HOUBENWEYL

[7] Semisynthetic derivatives of madurahydroxylactone and their antibacterial activities [J].

Heinisch, L ;

Roemer, E ;

Jütten, P ;

Haas, W ;

Werner, W ;

Möllmann, U .

JOURNAL OF ANTIBIOTICS, 1999, 52 (11) :1029-1041

[8] ESTRONE SULFAMATES - POTENT INHIBITORS OF ESTRONE SULFATASE WITH THERAPEUTIC POTENTIAL [J].

HOWARTH, NM ;

PUROHIT, A ;

REED, MJ ;

POTTER, BVL .

JOURNAL OF MEDICINAL CHEMISTRY, 1994, 37 (02) :219-221

[9] Development of (p-O-sulfamoyl)-N-alkanoyl-phenylalkyl amines as non-steroidal estrone sulfatase inhibitors [J].

Kolli, A ;

Chu, GH ;

Rhodes, ME ;

Inoue, K ;

Selcer, KW ;

Li, PK .

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 1999, 68 (1-2) :31-40

[10] THE HENS FERTILE EGG SCREENING-TEST (HEST) - A COMPARISON BETWEEN THE ACUTE TOXICITY FOR CHICK-EMBRYOS AND RODENTS OF 20 DRUGS [J].

NISHIGORI, H ;

MIZUMURA, M ;

IWATSURU, M .

CELL BIOLOGY AND TOXICOLOGY, 1992, 8 (04) :255-265