Antifungal Drug Discovery: Something Old and Something New

PLoS Pathogens

Volumn 8, Issue 9, 2012, Pages

  Butts, Arielle ^a   Krysan, Damian J ^b  

^a UNIVERSITY OF ROCHESTER   (United States)

^b UNIVERSITY OF ROCHESTER MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 AMINO N [4 [5 (2 PHENANTHRENYL) 3 TRIFLUOROMETHYL 1H PYRAZOL 1 YL]PHENYL]ACETAMIDE; AMPHOTERICIN B; ANTIFUNGAL AGENT; ANTINEOPLASTIC AGENT; CALCINEURIN; CASPOFUNGIN; D75 4590; E 1210; ECHINOCANDIN; ENOXACIN; FLUCONAZOLE; FLUCYTOSINE; GELDENAMYCIN DERIVATIVE; HEAT SHOCK PROTEIN 90 INHIBITOR; ISOXAZOLE DERIVATIVE; MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; PENICILLIC ACID; PHOSPHOINOSITIDE DEPENDENT KINASE 1 INHIBITOR; PHOSPHOTRANSFERASE INHIBITOR; SERTRALINE; TAMOXIFEN; UNCLASSIFIED DRUG;

ANTIFUNGAL ACTIVITY; ARTICLE; ASPERGILLUS FUMIGATUS; CANDIDA ALBICANS; CRYPTOCOCCAL MENINGITIS; CRYPTOCOCCOSIS; CRYPTOCOCCUS GATTII; CRYPTOCOCCUS NEOFORMANS; DRUG COST; DRUG DEVELOPMENT; DRUG EFFICACY; DRUG SCREENING; DRUG STRUCTURE; GALLERIA MELLONELLA; HUMAN; IMMUNE SYSTEM; IN VITRO STUDY; INVASIVE CANDIDIASIS; MONOTHERAPY; MORTALITY; NONHUMAN; PATIENT COMPLIANCE; PATIENT SAFETY; SACCHAROMYCES CEREVISIAE; SYSTEMIC MYCOSIS;

ANTIFUNGAL AGENTS; CELL WALL; DRUG DISCOVERY; DRUG REPOSITIONING; HEALTH SERVICES NEEDS AND DEMAND; HUMANS; MICROBIAL SENSITIVITY TESTS; MODELS, BIOLOGICAL; MOLECULAR TARGETED THERAPY; MYCOSES;

EID: 84866953429     PISSN: 15537366     EISSN: 15537374     Source Type: Journal    
DOI: 10.1371/journal.ppat.1002870     Document Type: Article

References (19)

1. Lai CC, Tan CK, Huang YT, Shao PL, Hsueh PR, (2008) Current challenges in the management of invasive fungal infections. J Infect Chemother 14: 77-85.
2. Park BJ, Wannemuehler KA, Marston BJ, Govender N, Pappas PG, et al. (2009) Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS. AIDS 23: 525-530.
3. Brown GD, Dennings DW, Levitz SM, (2012) Tackling human fungal infections. Science 336: 647.
4. Blankenship JR, Steinbach WJ, Perfect JR, Heitman J, (2003) Teaching old drugs new tricks: reincarnating immunosuppressants as antifungal drugs. Curr Opin Investig Drugs 4: 192-199.
5. Cowen LE, Singh SD, Kohler JR, Collins C, Zaas AK, et al. (2009) Harnessing Hsp90 function as a powerful, broadly effective therapeutic strategy for fungal infectious disease. Proc Natl Acad Sci U S A 106: 2818-2823.
6. Zhai B, Wu C, Wang L, Sachs MS, Lin X, (2012) The antidepressant sertraline provides a promising therapeutic option for neurotropic cryptococcal infections. Antimicrob Agents Chemother 56: 3758-3766.
7. Breger J, Fuchs BB, Aperis G, Moy TI, Ausubel FM, et al. (2007) Antifungal chemical compounds identified using a C. elegans pathogenicity assay. PLoS Pathog 3: e18 doi:10.1371/journal.ppat.0030018.
8. Spitzer M, Griffiths E, Blakely KM, Wildenhain J, Ejim L, et al. (2011) Cross-species discovery of syncretic drug combinations that potentiate the antifungal fluconazole. Mol Syst Biol 7: 499.
9. Roemer T, Xu D, Singh SB, Parish CA, Harris G, et al. (2011) Confronting the challenges of natural product-based antifungal discovery. Chem Biol 18: 148-164.
10. Tebbets B, Stewart D, Lawry S, Nett J, Nantel A, et al. (2012) Identification and characterization of antifungal compounds using a saccharomyces cerevisiae reporter bioassay. PLoS ONE 7: e36021 doi:10.1371/journal.pone.0036021.
11. Krysan DJ, Didone L, (2008) A high-throughput screening assay for small molecules that disrupt yeast cell integrity. J Biomol Screen 13: 657-664.
12. Wiseman H, Cannon M, Arnstein HR, (1989) Observation and significance of growth inhibition of Saccharomyces cerevisiae (A224A) by the anti-oestrogen drug tamoxifen. Biochem Soc Trans 17: 1038-1039.
13. Dolan K, Montgomery S, Buchheit B, Didone L, Wellington M, et al. (2009) Antifungal activity of tamoxifen: in vitro and in vivo activities and mechanistic characterization. Antimicrob Agents Chemother 53: 3337-3346.
14. Walker SS, Xu Y, Triantafyllou I, Waldman MF, Mendrick C, et al. (2011) Discovery of a novel class of orally active antifungal beta-1,3-D-glucan synthase inhibitors. Antimicrob Agents Chemother 55: 5099-5106.
15. Kitamura A, Someya K, Hata M, Nakajima R, Takemura M, (2009) Discovery of a small-molecule inhibitor of {beta}-1,6-glucan synthesis. Antimicrob Agents Chemother 53: 670-677.
16. Miyazaki M, Horii T, Hata K, Watanabe NA, Nakamoto K, et al. (2011) In vitro activity of E1210, a novel antifungal, against clinically important yeasts and molds. Antimicrob Agents Chemother 55: 4652-4658.
17. Hata K, Horii T, Miyazaki M, Watanabe NA, Okubo M, et al. (2011) Efficacy of oral E1210, a new broad-spectrum antifungal with a novel mechanism of action, in murine models of candidiasis, aspergillosis, and fusariosis. Antimicrob Agents Chemother 55: 4543-4551.
18. McLellan CA, Whitesell L, King OD, Lancaster AK, Mazitschek R, et al. (2012) Inhibiting GPI anchor biosynthesis in fungi stress the endoplasmic reticulum and enhances immunogencity. ACS Chem Biol. E-pub ahead of print doi.org/10.1021/cb300235m.
19. Baxter BK, DiDone L, Ogu D, Schor S, Krysan DJ, (2011) Identification, in vitro activity and mode of action of phosphoinositide-dependent-1 kinase inhibitors as antifungal molecules. ACS Chem Biol 6: 502-510.