Inhibitors of dihydrofolate reductase in leishmania and trypanosomes

被引：93

作者：

Gilbert, IH ^{[1
]}

机构：

[1] Cardiff Univ, Welsh Sch Pharm, Cardiff CF10 3XF, S Glam, Wales

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE | 2002年 / 1587卷 / 2-3期

关键词：

dihydrofolate reductase; Trypanosoma cruzi; Trypanosoma brucei; Leishmania;

D O I：

10.1016/S0925-4439(02)00088-1

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The protozoan diseases leishmaniasis, Chagas' disease and African trypanosomiasis are major health problems in many countries, particularly developing countries, and there are few drugs available to treat these diseases. Dihydrofolate reductase (DHFR) inhibitors have been used successfully in the treatment of a number of other diseases such as cancer, malaria and bacterial infections; however they have not been used for the treatment of these diseases. This article summarises studies on leishmanial and trypanosomal DHFR inhibitor development and evaluation. Possible mechanisms of resistance to DHFR inhibitors are also discussed. (C) 2002 Elsevier Science B.V All rights reserved.

引用

页码：249 / 257

页数：9

共 38 条

[1] Recent advances in identifying and validating drug targets in trypanosomes and leishmanias [J].

Barrett, MP ;

Mottram, JC ;

Coombs, GH .

TRENDS IN MICROBIOLOGY, 1999, 7 (02) :82-88

[2] PTR1 - A REDUCTASE MEDIATING SALVAGE OF OXIDIZED PTERIDINES AND METHOTREXATE RESISTANCE IN THE PROTOZOAN PARASITE LEISHMANIA-MAJOR [J].

BELLO, AR ;

NARE, B ;

FREEDMAN, D ;

HARDY, L ;

BEVERLEY, SM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (24) :11442-11446

[3] ANTILEISHMANIAL ACTIVITIES OF 2,4-DIAMINOQUINAZOLINE PUTATIVE DIHYDROFOLATE-REDUCTASE INHIBITORS [J].

BERMAN, JD ;

KING, M ;

EDWARDS, N .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1989, 33 (11) :1860-1863

[4] STRUCTURE ACTIVITY RELATIONSHIPS OF DIHYDROFOLATE-REDUCTASE INHIBITORS [J].

BLANEY, JM ;

HANSCH, C ;

SILIPO, C ;

VITTORIA, A .

CHEMICAL REVIEWS, 1984, 84 (04) :333-407

[5] QUANTITATIVE STRUCTURE ACTIVITY RELATIONSHIP OF TRIAZINE ANTIFOLATE INHIBITION OF LEISHMANIA DIHYDROFOLATE-REDUCTASE AND CELL-GROWTH [J].

BOOTH, RG ;

SELASSIE, CD ;

HANSCH, C ;

SANTI, DV .

JOURNAL OF MEDICINAL CHEMISTRY, 1987, 30 (07) :1218-1224

[6] Novel inhibitors of Leishmanial dihydrofolate reductase [J].

Chowdhury, SF ;

Di Lucrezia, R ;

Guerrero, RH ;

Brun, R ;

Goodman, J ;

Ruiz-Perez, LM ;

Pacanowska, DG ;

Gilbert, IH .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2001, 11 (08) :977-980

[7] Design, synthesis, and evaluation of inhibitors of trypanosomal and leishmanial dihydrofolate reductase [J].

Chowdhury, SF ;

Villamor, VB ;

Guerrero, RH ;

Leal, I ;

Brun, R ;

Croft, SL ;

Goodman, JM ;

Maes, L ;

Ruiz-Perez, LM ;

Pacanowska, DG ;

Gilbert, IH .

JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (21) :4300-4312

[8] Pteridine salvage throughout the Leishmania infectious cycle:: implications for antifolate chemotherapy [J].

Cunningham, ML ;

Beverley, SM .

MOLECULAR AND BIOCHEMICAL PARASITOLOGY, 2001, 113 (02) :199-213

[9] Regulation of differentiation to the infective stage of the protozoan parasite Leishmania major by tetrahydrobiopterin [J].

Cunningham, ML ;

Titus, RG ;

Turco, SJ ;

Beverley, SM .

SCIENCE, 2001, 292 (5515) :285-287

[10] ANTIMALARIAL DRUGS .24. FOLATE ANTAGONISTS .2. 2,4-DIAMINO-6-[[ARALKYL AND (HETEROCYCLIC)METHYL]AMINO]QUINAZOLINES, A NOVEL CLASS OF ANTIMETABOLITES OF INTEREST IN DRUG-RESISTANT MALARIA AND CHAGAS-DISEASE [J].

DAVOLL, J ;

DAVIES, HJ ;

CLARKE, J ;

BIRD, OD ;

ELSLAGER, EF ;

JOHNSON, AM .

JOURNAL OF MEDICINAL CHEMISTRY, 1972, 15 (08) :812-&

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