Literature DB >> 19560363

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

Janet L Paulsen1, Jieying Liu, David B Bolstad, Adrienne E Smith, Nigel D Priestley, Dennis L Wright, Amy C Anderson.   

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.

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Year:  2009        PMID： 19560363      PMCID： PMC2724765          DOI： 10.1016/j.bmc.2009.06.021

Source DB:  PubMed          Journal:  Bioorg Med Chem        ISSN： 0968-0896            Impact factor:   3.641


  16 in total

1.  X-Ray crystal structures of Candida albicans dihydrofolate reductase: high resolution ternary complexes in which the dihydronicotinamide moiety of NADPH is displaced by an inhibitor.

Authors:  M Whitlow; A J Howard; D Stewart; K D Hardman; J H Chan; D P Baccanari; R L Tansik; J S Hong; L F Kuyper
Journal:  J Med Chem       Date:  2001-08-30       Impact factor: 7.446

2.  Surflex: fully automatic flexible molecular docking using a molecular similarity-based search engine.

Authors:  Ajay N Jain
Journal:  J Med Chem       Date:  2003-02-13       Impact factor: 7.446

Review 3.  Rare and emerging opportunistic fungal pathogens: concern for resistance beyond Candida albicans and Aspergillus fumigatus.

Authors:  M A Pfaller; D J Diekema
Journal:  J Clin Microbiol       Date:  2004-10       Impact factor: 5.948

4.  X-ray crystallographic studies of Candida albicans dihydrofolate reductase. High resolution structures of the holoenzyme and an inhibited ternary complex.

Authors:  M Whitlow; A J Howard; D Stewart; K D Hardman; L F Kuyper; D P Baccanari; M E Fling; R L Tansik
Journal:  J Biol Chem       Date:  1997-11-28       Impact factor: 5.157

5.  Incidence of bloodstream infections due to Candida species and in vitro susceptibilities of isolates collected from 1998 to 2000 in a population-based active surveillance program.

Authors:  Rana A Hajjeh; Andre N Sofair; Lee H Harrison; G Marshall Lyon; Beth A Arthington-Skaggs; Sara A Mirza; Maureen Phelan; Juliette Morgan; Wendy Lee-Yang; Meral A Ciblak; Lynette E Benjamin; Laurie Thomson Sanza; Sharon Huie; Siew Fah Yeo; Mary E Brandt; David W Warnock
Journal:  J Clin Microbiol       Date:  2004-04       Impact factor: 5.948

6.  Secular trends in nosocomial primary bloodstream infections in the United States, 1980-1989. National Nosocomial Infections Surveillance System.

Authors:  S N Banerjee; T G Emori; D H Culver; R P Gaynes; W R Jarvis; T Horan; J R Edwards; J Tolson; T Henderson; W J Martone
Journal:  Am J Med       Date:  1991-09-16       Impact factor: 4.965

7.  Nosocomial infection rates in adult and pediatric intensive care units in the United States. National Nosocomial Infections Surveillance System.

Authors:  W R Jarvis; J R Edwards; D H Culver; J M Hughes; T Horan; T G Emori; S Banerjee; J Tolson; T Henderson; R P Gaynes
Journal:  Am J Med       Date:  1991-09-16       Impact factor: 4.965

8.  Selective inhibitors of Candida albicans dihydrofolate reductase: activity and selectivity of 5-(arylthio)-2,4-diaminoquinazolines.

Authors:  J H Chan; J S Hong; L F Kuyper; D P Baccanari; S S Joyner; R L Tansik; C M Boytos; S K Rudolph
Journal:  J Med Chem       Date:  1995-09-01       Impact factor: 7.446

9.  High-affinity inhibitors of dihydrofolate reductase: antimicrobial and anticancer activities of 7,8-dialkyl-1,3-diaminopyrrolo[3,2-f]quinazolines with small molecular size.

Authors:  L F Kuyper; D P Baccanari; M L Jones; R N Hunter; R L Tansik; S S Joyner; C M Boytos; S K Rudolph; V Knick; H R Wilson; J M Caddell; H S Friedman; J C Comley; J N Stables
Journal:  J Med Chem       Date:  1996-02-16       Impact factor: 7.446

10.  Synthetic and crystallographic studies of a new inhibitor series targeting Bacillus anthracis dihydrofolate reductase.

Authors:  Jennifer M Beierlein; Kathleen M Frey; David B Bolstad; Phillip M Pelphrey; Tammy M Joska; Adrienne E Smith; Nigel D Priestley; Dennis L Wright; Amy C Anderson
Journal:  J Med Chem       Date:  2008-12-11       Impact factor: 7.446
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  7 in total

1.  Crystal structures of Candida albicans dihydrofolate reductase bound to propargyl-linked antifolates reveal the flexibility of active site loop residues critical for ligand potency and selectivity.

Authors:  Janet L Paulsen; Stephen D Bendel; Amy C Anderson
Journal:  Chem Biol Drug Des       Date:  2011-07-29       Impact factor: 2.817

2.  Acetylenic linkers in lead compounds: a study of the stability of the propargyl-linked antifolates.

Authors:  Wangda Zhou; Kishore Viswanathan; Dennis Hill; Amy C Anderson; Dennis L Wright
Journal:  Drug Metab Dispos       Date:  2012-07-18       Impact factor: 3.922

3.  2,4-Diamino-5-(2'-arylpropargyl)pyrimidine derivatives as new nonclassical antifolates for human dihydrofolate reductase inhibition.

Authors:  Oztekin Algul; Janet L Paulsen; Amy C Anderson
Journal:  J Mol Graph Model       Date:  2010-11-11       Impact factor: 2.518

4.  Scoring ensembles of docked protein:ligand interactions for virtual lead optimization.

Authors:  Janet L Paulsen; Amy C Anderson
Journal:  J Chem Inf Model       Date:  2009-12       Impact factor: 4.956

5.  Structural analysis of the active sites of dihydrofolate reductase from two species of Candida uncovers ligand-induced conformational changes shared among species.

Authors:  Janet L Paulsen; Kishore Viswanathan; Dennis L Wright; Amy C Anderson
Journal:  Bioorg Med Chem Lett       Date:  2013-01-11       Impact factor: 2.823

6.  Propargyl-linked antifolates are dual inhibitors of Candida albicans and Candida glabrata.

Authors:  Narendran G-Dayanandan; Janet L Paulsen; Kishore Viswanathan; Santosh Keshipeddy; Michael N Lombardo; Wangda Zhou; Kristen M Lamb; Adrienne E Sochia; Jeremy B Alverson; Nigel D Priestley; Dennis L Wright; Amy C Anderson
Journal:  J Med Chem       Date:  2014-03-06       Impact factor: 7.446

7.  Dihydrofolate Reductase Is a Valid Target for Antifungal Development in the Human Pathogen Candida albicans.

Authors:  Christian DeJarnette; Arturo Luna-Tapia; Leanna R Estredge; Glen E Palmer
Journal:  mSphere       Date:  2020-06-24       Impact factor: 4.389
  7 in total

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