The structure-based design and synthesis of selective inhibitors of Trypanosoma cruzi dihydrofolate reductase.

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Zuccotto F, Brun R, Gonzalez Pacanowska D, Ruiz Perez LM, Gilbert IH

The structure-based design and synthesis of selective inhibitors of Trypanosoma cruzi dihydrofolate reductase.

Bioorg Med Chem Lett. 1999 May 17;9(10):1463-8.

PubMed ID

10360757 [ View in PubMed

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Abstract

This paper describes the design and synthesis of potential inhibitors of Trypanosoma cruzi dihydrofolate reductase using a structure-based approach. A model of the structure of the T. cruzi enzyme was compared with the structure of the human enzyme. The differences were used to design modifications of methotrexate to produce compounds which should be selective for the parasite enzyme. The derivatives of methotrexate were synthesised and tested against the enzyme and intact parasites.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Methotrexate	Dihydrofolate reductase	Ki (nM)	0.179	N/A	N/A	Details
Methotrexate	Dihydrofolate reductase	Ki (nM)	0.038	N/A	N/A	Details