In vitro biological activity and structural analysis of 2,4-diamino-5-(2′-arylpropargyl)pyrimidine inhibitors of Candida albicans

Janet L. Paulsen, Jieying Liu, David B. Bolstad, Adrienne E. Smith, Nigel D. Priestley, Dennis L. Wright, Amy C. Anderson

Research output: Contribution to journalArticlepeer-review

Abstract

In order to develop new antifungal agents effective against two species of Candida, we have designed a series of dihydrofolate reductase (DHFR) inhibitors. Here, we explore the structure-activity relationships of these inhibitors toward Candida albicans DHFR by evaluating enzyme inhibition, antifungal activity and toxicity to mammalian cells. Analysis of docked complexes of the enzyme and inhibitors yields the structural basis of relative potency. The meta-biphenyl series of this class exhibits the greatest enzyme inhibition, selectivity and antifungal activity.

Original languageEnglish
Pages (from-to)4866-4872
Number of pages7
JournalBioorganic and Medicinal Chemistry
Volume17
Issue number14
DOIs
StatePublished - Jul 15 2009

Keywords

  • Antifolate
  • Candida albicans
  • Dihydrofolate reductase
  • Molecular modeling

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