Inhibitors of de novo folate enzymes in Plasmodium falciparum

Alexis Nzila

doi:10.1016/j.drudis.2006.08.003

Inhibitors of de novo folate enzymes in Plasmodium falciparum

Alexis Nzila^*

^*Corresponding author for this work

Research output: Contribution to journal › Review article › peer-review

61 Scopus citations

Abstract

Antifolates, inhibitors of folate synthesis or folate conversion, are used for malaria treatment. They are developed as synergistic combinations of inhibitors of dihydrofolate reductase (DHFR) and of dihydropteroate synthase (DHPS). DHPS inhibitors are sulfur-based drugs, analogs of sulfanilamide. These compounds compete with para-aminobenzoic acid in the active site of DHPS. The discovery of new antifolates is based on the identification of DHFR inhibitors; little work has been done on sulfur-based drugs because of their toxicity. As a result, only a few sulfur-based drugs are available. In this review, the hypothesis that compounds that compete with pteridine derivatives in active sites of de novo folate enzymes can be used as synergizers of DHFR inhibitors is discussed. If correct, this could lead to the identification of a new family of synergizers of DHFR inhibitors.

Original language	English
Pages (from-to)	939-944
Number of pages	6
Journal	Drug Discovery Today
Volume	11
Issue number	19-20
DOIs	https://doi.org/10.1016/j.drudis.2006.08.003
State	Published - Oct 2006
Externally published	Yes

Bibliographical note

Funding Information:
We thank the director of the Kenya Medical Research Institute for permission to publish this review. The author thanks the European Developing Countries Clinical Trials Partnership (EDCTP) for financial support. Alexis Nzila is an EDCTP senior fellow.

UN SDGs

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

SDG 3 Good Health and Well-being

ASJC Scopus subject areas

Pharmacology
Drug Discovery

Access to Document

10.1016/j.drudis.2006.08.003

Cite this

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title = "Inhibitors of de novo folate enzymes in Plasmodium falciparum",

abstract = "Antifolates, inhibitors of folate synthesis or folate conversion, are used for malaria treatment. They are developed as synergistic combinations of inhibitors of dihydrofolate reductase (DHFR) and of dihydropteroate synthase (DHPS). DHPS inhibitors are sulfur-based drugs, analogs of sulfanilamide. These compounds compete with para-aminobenzoic acid in the active site of DHPS. The discovery of new antifolates is based on the identification of DHFR inhibitors; little work has been done on sulfur-based drugs because of their toxicity. As a result, only a few sulfur-based drugs are available. In this review, the hypothesis that compounds that compete with pteridine derivatives in active sites of de novo folate enzymes can be used as synergizers of DHFR inhibitors is discussed. If correct, this could lead to the identification of a new family of synergizers of DHFR inhibitors.",

author = "Alexis Nzila",

note = "Funding Information: We thank the director of the Kenya Medical Research Institute for permission to publish this review. The author thanks the European Developing Countries Clinical Trials Partnership (EDCTP) for financial support. Alexis Nzila is an EDCTP senior fellow.",

year = "2006",

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AU - Nzila, Alexis

N1 - Funding Information: We thank the director of the Kenya Medical Research Institute for permission to publish this review. The author thanks the European Developing Countries Clinical Trials Partnership (EDCTP) for financial support. Alexis Nzila is an EDCTP senior fellow.

PY - 2006/10

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N2 - Antifolates, inhibitors of folate synthesis or folate conversion, are used for malaria treatment. They are developed as synergistic combinations of inhibitors of dihydrofolate reductase (DHFR) and of dihydropteroate synthase (DHPS). DHPS inhibitors are sulfur-based drugs, analogs of sulfanilamide. These compounds compete with para-aminobenzoic acid in the active site of DHPS. The discovery of new antifolates is based on the identification of DHFR inhibitors; little work has been done on sulfur-based drugs because of their toxicity. As a result, only a few sulfur-based drugs are available. In this review, the hypothesis that compounds that compete with pteridine derivatives in active sites of de novo folate enzymes can be used as synergizers of DHFR inhibitors is discussed. If correct, this could lead to the identification of a new family of synergizers of DHFR inhibitors.

AB - Antifolates, inhibitors of folate synthesis or folate conversion, are used for malaria treatment. They are developed as synergistic combinations of inhibitors of dihydrofolate reductase (DHFR) and of dihydropteroate synthase (DHPS). DHPS inhibitors are sulfur-based drugs, analogs of sulfanilamide. These compounds compete with para-aminobenzoic acid in the active site of DHPS. The discovery of new antifolates is based on the identification of DHFR inhibitors; little work has been done on sulfur-based drugs because of their toxicity. As a result, only a few sulfur-based drugs are available. In this review, the hypothesis that compounds that compete with pteridine derivatives in active sites of de novo folate enzymes can be used as synergizers of DHFR inhibitors is discussed. If correct, this could lead to the identification of a new family of synergizers of DHFR inhibitors.

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DO - 10.1016/j.drudis.2006.08.003

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AN - SCOPUS:33748746654

SN - 1359-6446

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JF - Drug Discovery Today

IS - 19-20

ER -

Inhibitors of de novo folate enzymes in Plasmodium falciparum

Abstract

Bibliographical note

UN SDGs

ASJC Scopus subject areas

Access to Document

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