The purine transferase from Trypanosoma cruzi as a potential target for bisphosphonate-based chemotherapeutic compounds

被引：10

作者：

Fernández, D

Wenck, MA

Craig, SP

Delfino, JM

机构：

[1] Univ Buenos Aires, Fac Farm & Bioquim, Dept Quim Biol, RA-1113 Buenos Aires, DF, Argentina

[2] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA

[3] Univ Connecticut, Storrs, CT 06269 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 17期

关键词：

bisphosphonates; Chagas; HPRT inhibitors; Trypanosoma cruzi;

D O I：

10.1016/j.bmcl.2004.06.042

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We identified and tested bisphosphonates as inhibitors of a protozoan molecular target. Computational modeling studies demonstrated that these compounds are mimics of the natural substrate of the enzyme. The most potent bisphosphonates in vitro are pamidronate and risedronate, which inhibit the purine transferase from Trypanosoma cruzi in the micromolar range. (C) 2004 Elsevier Ltd. All rights reserved.

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页码：4501 / 4504

页数：4

相关论文

共 31 条

[1] The Cambridge Structural Database: a quarter of a million crystal structures and rising [J].

Allen, FH .

ACTA CRYSTALLOGRAPHICA SECTION B-STRUCTURAL SCIENCE, 2002, 58 (3 PART 1) :380-388

[2] Rational design of selective submicromolar inhibitors of Tritrichomonas foetus hypoxanthine-guanine-xanthine phosphoribosyltransferase [J].

Aronov, AM ;

Munagala, NR ;

de Montellano, PRO ;

Kuntz, ID ;

Wang, CC .

BIOCHEMISTRY, 2000, 39 (16) :4684-4691

[3] Pharmacokinetics of pamidronate disodium in patients with cancer with normal or impaired renal function [J].

Berenson, JR ;

Rosen, L ;

Vescio, R ;

Lau, HS ;

Woo, M ;

Sioufi, A ;

Kowalski, O ;

Knight, RD ;

Seaman, JJ .

JOURNAL OF CLINICAL PHARMACOLOGY, 1997, 37 (04) :285-290

[4] AN INTERNAL COORDINATE MONTE-CARLO METHOD FOR SEARCHING CONFORMATIONAL SPACE [J].

CHANG, G ;

GUIDA, WC ;

STILL, WC .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1989, 111 (12) :4379-4386

[5] Purine phosphoribosyltransferases [J].

Craig, SP ;

Eakin, AE .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (27) :20231-20234

[6]

Dunford JE, 2001, J PHARMACOL EXP THER, V296, P235

[7] Hypoxanthine phosphoribosyltransferase from Trypanosoma cruzi as a target for structure-based inhibitor design: Crystallization and inhibition studies with purine analogs [J].

Eakin, AE ;

Guerra, A ;

Focia, PJ ;

TorresMartinez, J ;

Craig, SP .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1997, 41 (08) :1686-1692

[8] Potential chemotherapeutic targets in the purine metabolism of parasites [J].

el Kouni, MH .

PHARMACOLOGY & THERAPEUTICS, 2003, 99 (03) :283-309

[9]

FERNANDEZ D, 2002, ACTA CRYST C, V58

[10] Approaching the transition state in the crystal structure of a phosphoribosyltransferase [J].

Focia, PJ ;

Craig, SP ;

Eakin, AE .

BIOCHEMISTRY, 1998, 37 (49) :17120-17127

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