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Towards species-specific antifolates.

D C M Chan1, A C Anderson

  • 1Dartmouth College, Department of Chemistry, Burke Laboratories, Hanover, New Hampshire 03755, USA.

Current Medicinal Chemistry
|February 16, 2006
PubMed
Summary
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New antifolates targeting dihydrofolate reductase (DHFR) are crucial for combating drug-resistant microbes. This review highlights advances in developing species-selective DHFR inhibitors for infectious diseases like malaria.

Area of Science:

  • Biochemistry
  • Medicinal Chemistry
  • Parasitology

Background:

  • Dihydrofolate reductase (DHFR) is a vital enzyme and a long-standing drug target.
  • Existing antifolates (e.g., methotrexate) are used for cancer, bacterial, fungal, and parasitic infections.
  • Emerging drug resistance and new disease threats necessitate novel, selective antifolates.

Purpose of the Study:

  • To review recent progress in developing species-selective antifolate inhibitors.
  • To focus on advances against DHFR from key pathogens: *Pneumocystis jirovecii* and *Plasmodium falciparum*.

Main Methods:

  • Literature review of recent studies on antifolate drug development.
  • Analysis of strategies for achieving species selectivity in DHFR inhibition.
  • Case studies focusing on *P. jirovecii* and *P. falciparum* inhibitors.

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Main Results:

  • Several new antifolates show species-specific potency against DHFR.
  • Challenges remain in achieving broad potency and selectivity simultaneously.
  • Progress has been made in targeting DHFR from *P. jirovecii* and *P. falciparum*.

Conclusions:

  • Developing species-selective DHFR inhibitors is critical for new antimicrobial and antiparasitic therapies.
  • Targeting specific DHFR enzymes offers a promising strategy against resistant pathogens.
  • Continued research is needed to overcome challenges in antifolate selectivity and potency.