Targeting DHFR in parasitic protozoa

被引：118

作者：

Anderson, AC ^{[1
]}

机构：

[1] Dartmouth Coll, Dept Chem, Hanover, NH 03755 USA

来源：

DRUG DISCOVERY TODAY | 2005年 / 10卷 / 02期

关键词：

D O I：

10.1016/S1359-6446(04)03308-2

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Parasitic apicomplexans are responsible for some of the most severe worldwide health problems, including malaria, toxoplasmosis and cryptosporidiosis. These parasites are characterized by a bifunctional enzyme, dihydrofolate reductase-thymidylate synthase (DHFR-TS), which has a crucial role in pyrimidine biosynthesis. Inhibitors of DHFR have been successful in the treatment of toxoplasmosis and malaria. However, there is currently no effective therapy for cryptosporidiosis, and despite early successes against malaria, resistance to DHFR inhibitors in malaria parasites has now become a global problem. Novel DHFR inhibitors, designed using the recently revealed crystal structures of the enzymes from two parasitic protozoa, are in development.

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页码：121 / 128

页数：8

相关论文

共 51 条

[11] Mechanisms of drug resistance in malaria [J].

Cowman, AF .

AUSTRALIAN AND NEW ZEALAND JOURNAL OF MEDICINE, 1995, 25 (06) :837-844

[12] STABLE MOLECULAR-TRANSFORMATION OF TOXOPLASMA-GONDII - A SELECTABLE DIHYDROFOLATE REDUCTASE-THYMIDYLATE SYNTHASE MARKER BASED ON DRUG-RESISTANCE MUTATIONS IN MALARIA [J].

DONALD, RGK ;

ROOS, DS .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (24) :11703-11707

[13] Epidemiology of Cryptosporidium:: transmission, detection and identification [J].

Fayer, R ;

Morgan, U ;

Upton, SJ .

INTERNATIONAL JOURNAL FOR PARASITOLOGY, 2000, 30 (12-13) :1305-1322

[14]

FLEMING GF, 1992, SEMIN ONCOL, V19, P707

[15] Sneaking in through the back entrance: the biology of malaria liver stages [J].

Frevert, U .

TRENDS IN PARASITOLOGY, 2004, 20 (09) :417-424

[16] Design, synthesis, and biological evaluation of 2,4-diamino-5-methyl-6-substituted-pyrrolo[2,3-d]pyrimidines as dihydrofolate reductase inhibitors [J].

Gangjee, A ;

Lin, X ;

Queener, SF .

JOURNAL OF MEDICINAL CHEMISTRY, 2004, 47 (14) :3689-3692

[17] Cryptosporidiosis: Are emerging, highly infectious threat [J].

Guerrant, RL .

EMERGING INFECTIOUS DISEASES, 1997, 3 (01) :51-57

[18] Novel alleles of the Plasmodium falciparum dhfr highly resistant to pyrimethamine and chlorcycloguanil, but not WR99210 [J].

Hankins, EG ;

Warhurst, DC ;

Sibley, CH .

MOLECULAR AND BIOCHEMICAL PARASITOLOGY, 2001, 117 (01) :91-102

[19]

Hayde M., 2000, CONGENITAL TOXOPLASM, P153

[20] Plasmodium falciparum: Kinetic interactions of WR99210 with pyrimethamine-sensitive and pyrimethamine-resistant dihydrofolate reductase [J].

HekmatNejad, M ;

Rathod, PK .

EXPERIMENTAL PARASITOLOGY, 1997, 87 (03) :222-228

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