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

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Paulsen JL, Liu J, Bolstad DB, Smith AE, Priestley ND, Wright DL, Anderson AC

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

Bioorg Med Chem. 2009 Jul 15;17(14):4866-72. doi: 10.1016/j.bmc.2009.06.021. Epub 2009 Jun 17.

PubMed ID
19560363 [ View in PubMed
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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.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
5-[(3R)-3-(5-methoxybiphenyl-3-yl)but-1-yn-1-yl]-6-methylpyrimidine-2,4-diamineDihydrofolate reductaseIC 50 (nM)1360N/AN/ADetails
5-[3-(2,5-dimethoxyphenyl)prop-1-yn-1-yl]-6-ethylpyrimidine-2,4-diamineDihydrofolate reductaseIC 50 (nM)1280N/AN/ADetails
TrimethoprimDihydrofolate reductaseIC 50 (nM)198000N/AN/ADetails