Novel inhibitors of Trypanosoma cruzi dihydrofolate reductase

Fabio Zuccotto; Marketa  Zvelebil; Reto  Brun; Shafinaz F. Chowdhury; Raffaella Di Lucrezia; Isabel Leal; Louis Maes; Luis M. Ruiz-Perez; Dolores Gonzalez Pacanowska; Ian H . Gilbert

doi:10.1016/S0223-5234(01)01235-1

Novel inhibitors of Trypanosoma cruzi dihydrofolate reductase

Fabio Zuccotto
, Marketa Zvelebil
, Reto Brun
, Shafinaz F. Chowdhury
, Raffaella Di Lucrezia
, Isabel Leal
, Louis Maes
, Luis M. Ruiz-Perez
, Dolores Gonzalez Pacanowska
, Ian H . Gilbert (Lead / Corresponding author)

Research output: Contribution to journal › Article › peer-review

72 Citations (Scopus)

Abstract

There is an urgent need for the development of new drugs to treat Chagas' disease, which is caused by the protozoan parasite Trypanosoma cruzi. The enzyme dihydrofolate reductase (DHFR) has been a very successful drug target in a number of diseases and we decided to investigate it as a potential drug target for Chagas' disease. A homology model of the enzyme was used to search the Cambridge Structural Database using the program DOCK 3.5. Compounds were then tested against the enzyme and the whole parasite. Compounds were also screened against the related parasite, Trypanosoma brucei.

Original language	English
Pages (from-to)	395-405
Number of pages	11
Journal	European Journal of Medicinal Chemistry
Volume	36
Issue number	5
DOIs	https://doi.org/10.1016/S0223-5234(01)01235-1
Publication status	Published - May 2001

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Animals
Cell Line
Chagas Disease
Databases as Topic
Disease Models, Animal
Drug Design
Drug Evaluation, Preclinical
Enzyme Inhibitors
Folic Acid Antagonists
Inhibitory Concentration 50
Mice
Muscles
Rats
Tetrahydrofolate Dehydrogenase
Trypanosoma brucei rhodesiense
Trypanosoma cruzi
Journal Article
Research Support, Non-U.S. Gov't

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10.1016/S0223-5234(01)01235-1

Cite this

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title = "Novel inhibitors of Trypanosoma cruzi dihydrofolate reductase",

abstract = "There is an urgent need for the development of new drugs to treat Chagas' disease, which is caused by the protozoan parasite Trypanosoma cruzi. The enzyme dihydrofolate reductase (DHFR) has been a very successful drug target in a number of diseases and we decided to investigate it as a potential drug target for Chagas' disease. A homology model of the enzyme was used to search the Cambridge Structural Database using the program DOCK 3.5. Compounds were then tested against the enzyme and the whole parasite. Compounds were also screened against the related parasite, Trypanosoma brucei.",

keywords = "Animals, Cell Line, Chagas Disease, Databases as Topic, Disease Models, Animal, Drug Design, Drug Evaluation, Preclinical, Enzyme Inhibitors, Folic Acid Antagonists, Inhibitory Concentration 50, Mice, Muscles, Rats, Tetrahydrofolate Dehydrogenase, Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Journal Article, Research Support, Non-U.S. Gov't",

author = "Fabio Zuccotto and Marketa Zvelebil and Reto Brun and Chowdhury, \{Shafinaz F.\} and \{Di Lucrezia\}, Raffaella and Isabel Leal and Louis Maes and Ruiz-Perez, \{Luis M.\} and Pacanowska, \{Dolores Gonzalez\} and Gilbert, \{Ian H .\}",

year = "2001",

month = may,

doi = "10.1016/S0223-5234(01)01235-1",

language = "English",

volume = "36",

pages = "395--405",

journal = "European Journal of Medicinal Chemistry",

issn = "0223-5234",

publisher = "Elsevier",

number = "5",

}

TY - JOUR

T1 - Novel inhibitors of Trypanosoma cruzi dihydrofolate reductase

AU - Zuccotto, Fabio

AU - Zvelebil, Marketa

AU - Brun, Reto

AU - Chowdhury, Shafinaz F.

AU - Di Lucrezia, Raffaella

AU - Leal, Isabel

AU - Maes, Louis

AU - Ruiz-Perez, Luis M.

AU - Pacanowska, Dolores Gonzalez

AU - Gilbert, Ian H .

PY - 2001/5

Y1 - 2001/5

N2 - There is an urgent need for the development of new drugs to treat Chagas' disease, which is caused by the protozoan parasite Trypanosoma cruzi. The enzyme dihydrofolate reductase (DHFR) has been a very successful drug target in a number of diseases and we decided to investigate it as a potential drug target for Chagas' disease. A homology model of the enzyme was used to search the Cambridge Structural Database using the program DOCK 3.5. Compounds were then tested against the enzyme and the whole parasite. Compounds were also screened against the related parasite, Trypanosoma brucei.

AB - There is an urgent need for the development of new drugs to treat Chagas' disease, which is caused by the protozoan parasite Trypanosoma cruzi. The enzyme dihydrofolate reductase (DHFR) has been a very successful drug target in a number of diseases and we decided to investigate it as a potential drug target for Chagas' disease. A homology model of the enzyme was used to search the Cambridge Structural Database using the program DOCK 3.5. Compounds were then tested against the enzyme and the whole parasite. Compounds were also screened against the related parasite, Trypanosoma brucei.

KW - Animals

KW - Cell Line

KW - Chagas Disease

KW - Databases as Topic

KW - Disease Models, Animal

KW - Drug Design

KW - Drug Evaluation, Preclinical

KW - Enzyme Inhibitors

KW - Folic Acid Antagonists

KW - Inhibitory Concentration 50

KW - Mice

KW - Muscles

KW - Rats

KW - Tetrahydrofolate Dehydrogenase

KW - Trypanosoma brucei rhodesiense

KW - Trypanosoma cruzi

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/S0223-5234(01)01235-1

DO - 10.1016/S0223-5234(01)01235-1

M3 - Article

C2 - 11451529

SN - 0223-5234

VL - 36

SP - 395

EP - 405

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

IS - 5

ER -

Novel inhibitors of Trypanosoma cruzi dihydrofolate reductase

Abstract

UN SDGs

Keywords

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