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ID: ALA1154109

Journal: Bioorg Med Chem

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

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

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.

CiteXplore: 19560363

DOI: 10.1016/j.bmc.2009.06.021