Oxidosqualene cyclase inhibitors as antimicrobial agents

被引：31

作者：

Hinshaw, JC

Suh, DY

Garnier, P

Buckner, FS

Eastman, RT

Matsuda, SPT

Joubert, BM

Coppens, I

Joiner, KA

Merali, S

Nash, TE

Prestwich, GD

机构：

[1] Univ Utah, Dept Med Chem, Salt Lake City, UT 84108 USA

[2] Univ Washington, Dept Med, Seattle, WA 98195 USA

[3] Rice Univ, Dept Chem, Houston, TX 77005 USA

[4] Rice Univ, Dept Biochem & Cell Biol, Houston, TX 77005 USA

[5] Yale Univ, Sch Med, Infect Dis Sect, Dept Internal Med, New Haven, CT 06520 USA

[6] NYU, Sch Med, Dept Med & Mol Parasitol, New York, NY 10010 USA

[7] NIH, Parasit Dis Lab, Bethesda, MD 20892 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2003年 / 46卷 / 20期

关键词：

D O I：

10.1021/jm034126t

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Small-molecule oxidosqualene cyclase (OSC) inhibitors were found to be effective in assays against cloned OSC-like enzymes from human pathogens. A combinatorial library was prepared and used to identify lead compounds that inhibit the growth of Trypanosoma cruzi, Leishmania mexicana amazonensis, and Pneumocystis carinii in culture. Selectivity for the microorganisms in preference to mammalian cells was observed.

引用

收藏

页码：4240 / 4243

页数：4

相关论文

共 34 条

[1] AFFINITY LABELING OF VERTEBRATE OXIDOSQUALENE CYCLASES WITH A TRITIATED SUICIDE SUBSTRATE [J].

ABE, I ;

BAI, M ;

XIAO, XY ;

PRESTWICH, GD .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1992, 187 (01) :32-38

[2]

Abe I., 1999, Comprehensive Natural Products Chemistry, VVolume 2, P267

[3] Structural and stereoelectronic requirements for the inhibition of mammalian 2,3-oxidosqualene cyclase by substituted isoquinoline derivatives [J].

Barth, MM ;

Binet, JL ;

Thomas, DM ;

deFornel, DC ;

Samreth, S ;

Schuber, FJ ;

Renaut, PP .

JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (12) :2302-2312

[4]

Brown GD, 1998, NAT PROD REP, V15, P653

[5] Novel 4-piperidinopyridine inhibitors of oxidosqualene cyclase-lanosterol synthase derived by consideration of inhibitor pKa [J].

Brown, GR ;

Foubister, AJ ;

Johnson, MC ;

Newcombe, NJ ;

Waterson, D ;

Wells, SL .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2001, 11 (16) :2213-2216

[6] Quinuclidine inhibitors of 2,3-oxidosqualene cyclase-lanosterol synthase: Optimization from lipid profiles [J].

Brown, GR ;

Hollinshead, DM ;

Stokes, ESE ;

Clarke, DS ;

Eakin, MA ;

Foubister, AJ ;

Glossop, SG ;

Griffiths, D ;

Johnson, MC ;

McTaggart, F ;

Mirrlees, DJ ;

Smith, GJ ;

Wood, R .

JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (07) :1306-1311

[7] A novel series of 4-piperidinopyridine and 4-piperidinopyrimidine inhibitors of 2,3-oxidosqualene cyclase-lanosterol synthase [J].

Brown, GR ;

Hollinshead, DM ;

Stokes, ESE ;

Waterson, D ;

Clarke, DS ;

Foubister, AJ ;

Glossop, SC ;

McTaggart, F ;

Mirrlees, DJ ;

Smith, GJ ;

Wood, R .

JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (26) :4964-4972

[8] Cloning and heterologous expression of the Trypanosoma brucei lanosterol synthase gene [J].

Buckner, FS ;

Nguyen, LN ;

Joubert, BM ;

Matsuda, SPT .

MOLECULAR AND BIOCHEMICAL PARASITOLOGY, 2000, 110 (02) :399-403

[9] Potent anti-Trypanosoma cruzi activities of oxidosqualene cyclase inhibitors [J].

Buckner, FS ;

Griffin, JH ;

Wilson, AJ ;

Van Voorhis, WC .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2001, 45 (04) :1210-1215

[10]

Chance Michael L., 1997, P163

← 1 2 3 4 →