A repurposing approach identifies off-patent drugs with fungicidal cryptococcal activity, a common structural chemotype, and pharmacological properties relevant to the treatment of Cryptococcosis

Eukaryotic Cell

Volumn 12, Issue 2, 2013, Pages 278-287

  Butts, Arielle ^a   DiDone, Louis ^b   Koselny, Kristy ^b   Baxter, Bonnie K ^b   Chabrier Rosello, Yeissa ^b   Wellington, Melanie ^b   Krysanb, 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

ADENYLATE KINASE; AMIODARONE; ANTIFUNGAL AGENT; CALMODULIN; FLUCONAZOLE; FUNGAL PROTEIN; SULOCTIDIL; THIORIDAZINE;

ANIMAL; ARTICLE; CELL CULTURE; CHEMICAL PHENOMENA; CRYPTOCOCCOSIS; CRYPTOCOCCUS NEOFORMANS; DRUG ANTAGONISM; DRUG EFFECT; DRUG POTENTIATION; HIGH THROUGHPUT SCREENING; HUMAN; METABOLISM; MICROBIAL SENSITIVITY TEST; MICROBIOLOGY; MOLECULAR LIBRARY; MOUSE; PATENT; PHAGOCYTE; STRUCTURE ACTIVITY RELATION;

ADENYLATE KINASE; AMIODARONE; ANIMALS; ANTIFUNGAL AGENTS; CALMODULIN; CELLS, CULTURED; CRYPTOCOCCOSIS; CRYPTOCOCCUS NEOFORMANS; DRUG SYNERGISM; FLUCONAZOLE; FUNGAL PROTEINS; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; HYDROPHOBIC AND HYDROPHILIC INTERACTIONS; MICE; MICROBIAL SENSITIVITY TESTS; PATENTS AS TOPIC; PHAGOCYTES; SMALL MOLECULE LIBRARIES; STRUCTURE-ACTIVITY RELATIONSHIP; SULOCTIDIL; THIORIDAZINE;

EID: 84873109558     PISSN: 15359778     EISSN: None     Source Type: Journal    
DOI: 10.1128/EC.00314-12     Document Type: Article

References (42)

1. Park BJ, Wannemuehler KA, Marston BJ, Govender N, Pappas PG, Chiller TM. 2009. Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS. AIDS 23:525-530.
2. Kwon-Chung KJ, Boekhout T, Wickes BL, Fell J. 2011. Systematics of the genus Cryptococcus and its type species C. neoformans, p 3-17. In Heitman J, Kozel TR, Kwon-Chung KJ, Perfect JR, Casadevall A (ed), Cryptococcus: from human pathogen to model yeast. ASM Press, Washington, DC.
3. Perfect JR. 2012. The triple threat of cryptococcosis: it's the body site, the strain and/or the host. mBio 3:e100165-12. doi:10.1128/mBio.00165-12.
4. Perfect JR, Dismukes WE, Dromer F, Goldman DL, Graybill JR, Hamill RJ, Harrison TS, Larsen RA, Lortholary O, Nguyen MH, Pappas PG, Powderly WG, Singh N, Sobel JD, Sorrell TC. 2010. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the Infectious Diseases Society of America. Clin. Infect. Dis. 50:291-322.
5. Sloan DJ, Dedicoat MJ, Lalloo DG. 2009. Treatment of cryptococcal meningitis in resource-limited settings. Curr. Opin. Infect. Dis. 22:455-463.
6. Bicanic T, Muzoora C, Brouwer AE, Meintjes G, Longley N, Taseera K, Rebe K, Loyse A, Jarivis J, Bekker LG, Wood R, Limmathurostakul D, Chierakul W, Stepniewska K, White NJ, Jaffar S, Harrison TS. 2009. Independent association of clearance of infection and clinical outcome of HIV-associated cryptococcal meningitis: analysis of combined cohort of 262 patients. Clin. Infect. Dis. 49:702-709.
7. Butts A, Krysan DJ. 2012. Antifungal drug discovery: something old and something new. PLoS Pathog. 8:e1002870. doi:10.1371/journal.ppat.1002870.
8. DiDone L, Scrimale T, Baxter BK, Krysan DJ. 2010. A high-throughput assay of yeast cell lysis for drug discovery and genetic analysis. Nat. Protoc. 5:1107-1114.
9. Bisson WH. 2012. Drug repurposing in chemical genomics: can we learn from the past to improve the future? Curr. Top. Med. Chem. 12:1883-1888.
10. Banks WA. 2009. Characteristics of drugs that cross the blood-brainbarrier. BMC Neurol. 9:53. doi:10.1186/1471-2377-9-53.
11. Nadanaciva S, Lu S, Gehard DF, Jessen BA, Pennie WA, Will Y. 2011. A high-content screening assay for identifying lysosomotropic compounds. Toxicol. In Vitro 25:715-723.
12. National Committee for Clinical Laboratory Standards. 2002. Reference method for broth dilution antifungal susceptibility testing of yeasts. Approved standard M27-A2. National Committee for Clinical Laboratory Standards, Wayne, PA.
13. Krysan DJ, DiDone L. 2008. A high-throughput screening assay for small molecules that disrupt yeast cell integrity. J. Biomol. Screen. 181:1073-1081.
14. Chabrier-Rosello Y, Gerik K, Koselny K, DiDone LL, Lodge JK, Krysan DJ. 19 October 2012. Cryptococcus neoformans phosphoinositidedependent kinase 1 (PDK1) ortholog is required for stress tolerance. Eukaryot. Cell doi:10.1128/EC.00235-12.
15. Kraus PR, Heitman J. 2003. Coping with stress: calmodulin and calcineurin in model and pathogenic fungi. Biochem. Biophys. Res. Commun. 311:1151-1157.
16. Gupta SS, Ton UK, Beaudry V, Rulli S, Cunningham K, Rao R. 2003. Antifungal activity of amiodarone is mediated by disruption of calcium homeostasis. J. Biol. Chem. 278:28831-28839.
17. Courchesne WE. 2002. Characterization of broad-based fungicidal activity for the antiarrhythmic drug amiodarone. J. Pharmacol. Exp. Ther. 300:195-199.
18. Gamarra S, Rocha EM, Zhang YQ, Parks S, Rao R, Perlin D. 2010. Mechanism of the synergistic effect of amiodarone and fluconazole in C. albicans. Antimicrob. Agents Chemother. 54:1753-1761.
19. Moend S, Rao R. 2008. Fungicidal activity of amiodarone is tightly coupled to calcium influx. FEMS Yeast Res. 8:425-431.
20. Pystowosky EN. 2010. Atrial fibrillation: dronedarone and amiodarone-the safety versus efficacy debate. Nat. Rev. Cardiol. 7:5-6.
21. Balgi AD, Fonesca BD, Donahue E, Tsang TCF, Lajoie P, Proud CG, Nabi IR, Roberge M. 2009. Screen for specific modulators of autophagy reveals novel therapeutic inhibitors of TORC1 signaling. PLoS One 4:e7124. doi:10.1371/journal.pone.0007124.
22. Zhang L, Yu J, Pan H, Hu P, Hao Y, Cai W, Zhu H, Yu AD, Xie X, Ma D, Yaun J. 2007. Small molecule regulators of autophagy identified by an image-based high-throughput screen. Proc. Natl. Acad. Sci. U. S. A. 104: 19023-19028.
23. Voelz K, May RC. 2010. Cryptococcal interactions with the host immune system. Eukaryot. Cell 9:835-846.
24. Herrmann JL, Dubois N, Fourgeaud M, Basset D, Lagrange PH. 1994. Synergic activity of amphotericin-B and gamma interferon against intracellular Cryptococcus neoformans in macrophages. J. Antimicrob. Chemother. 34:1051-1058.
25. Levitz SM, Harrison TS, Tabuni A, Liu X. 1997. Chloroquine induces human mononuclear phagocytes to inhibit and kill Cryptococcus neoformans by a mechanism independent of iron deprivation. J. Clin. Invest. 100:1640-1646.
26. Prozialeck WG, Weiss B. 1982. Inhibition of calmodulin by phenothiazines and related drugs: structure-activity relationships. J. Pharmacol. Exp. Ther. 222:509-516.
27. Dolan K, Montgomery S, Buchheit B, DiDone L, Wellington M, Krysan DJ. 2009. The antifungal activity of tamoxifen: in vitro, in vivo, and mechanistic characterization. Antimicrob. Agents Chemother. 53:3337-3346.
28. Mukherjee PK, Sheehan DJ, Hitchcock CA, Ghannoum MA. 2005. Combination treatment of invasive fungal infections. Clin. Microbiol. Rev. 8:163-194.
29. Spitzer M, Griffiths E, Blakely KM, Wildenhain J, Tyers M, Wright GD. 2011. Cross-species discovery of syncretic drug combinations that potentiate the antifungal fluconazole. Mol. Syst. Biol. 7:499. doi:10.1038/msb.2011.31.
30. Futamura Y. 1996. Effect of amiodarone on cytokine release and on enzyme activities of mouse alveolar macrophages, bone marrow macrophages, and blood monocytes. J. Toxicol. Sci. 21:125-134.
31. Ordway D, Viveiros L, Bettencourt R, Aleida J, Martins M, Kristiansen JE, Molnar J, Amaral L. 2003. Clinical concentrations of thioridazine kill intracellular multidrug-resistant Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 47:917-922.
32. Abbate E, Vescovo M, Natiello M, Cufre M, Garcia A, Gonzalez Montaner P, Ambroggi M, Ritacco V, van Soolingen D. 2012. Successful alternative treatment of extensively drug-resistant tuberculosis in Argentina with a combination of linezolid, moxifloxacin, and thioridazine. J. Antimicrob. Chemother. 67:473-477.
33. Bergling R, Mjondal T, Oreland L, Rapp W, Wold S. 1975. Plasma levels and clinical effects of thioridazine and thiothixene. J. Clin. Pharmacol. 15:178-186.
34. Benain B, Garcia CR. 2011. Targeting calcium homeostasis as a therapy of Chagas' disease and leishmaniasis-a review. Trop. Biomed. 28:471-481.
35. Senistenra G, Chau I, Vedad M. 2011. Thermal denaturation assays in chemical biology. Assay Drug Dev. Technol. 10:128-136.
36. Schaars CF, Meintjes GA, Mooroni C, Post FA, Maartens G. 2006. Outcome of AIDS-associated cryptococcal meningitis initially treated with 200mg/day and 400mg/day of fluconazole. BMC Infect. Dis. 6:118. doi:10.1186/1471-2334-6-118.
37. Del Poeta M, Cruz MC, Cardenas ME, Perfect JR, Heitman J. 2000. Synergistic antifungal activities of bafilomycin A(1), fluconazole, and the pneumocandin MC0991/caspofungin acetate (L-743,873) with calcineurin inhibitors FK506 and L-685,818 against Cryptococcus neoformans. Antimicrob. Agents Chemother. 44:739-746.
38. 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.
39. Zhai B, Zho J, Yang L, Zhang J, Jung K, Giam CZ, Xiang XL, Lin X. 2010. Polymixin B, in combination with fluconazole, exerts a potent fungicidal effect. J. Antimicrob. Chemother. 65:931-938.
40. Eilam Y, Polacheck I, Ben-Golgi B, Chernichovosky D. 1987. Activity of phenothiazines against medically important yeasts. Antimicrob. Agents Chemother. 31:834-836.
41. Ericson E, Bebbia M, Heisler LE, Wildenhain J, Tyers M, Giaver G, Nislow C. 2008. Off-target effects of psychoactive drugs revealed by genome-side assays in yeast. PLoS Genet. 4:e1000151. doi:10.1371/journal.pgen.1000151.
42. Pluta K, Morak-Moldanska B, Jelen M. 2011. Recent progress in biological activities of synthesized phenothiazines. Eur. J. Med. Chem. 46:3179-3189.