Recent Advances in Azole Based Scaffolds as Anticandidal Agents

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Abstract

Aim: The present review aims to explore the development of novel antifungal agents, such as pharmacology, pharmacokinetics, spectrum of activity, safety, toxicity and other aspects that involve drug-drug interactions of the azole antifungal agents.

Introduction: Fungal infections in critically ill and immune-compromised patients are increasing at alarming rates, caused mainly by Candida albicans an opportunistic fungus. Despite antifungal annihilators like amphotericin B, azoles and caspofungin, these infections are enormously increasing. The unconventional increase in such patients is a challenging task for the management of antifungal infections especially Candidiasis. Moreover, problem of toxicity associated with antifungal drugs on hosts and rise of drug-resistance in primary and opportunistic fungal pathogens has obstructed the success of antifungal therapy.

Conclusion: Hence, to conflict these problems new antifungal agents with advanced efficacy, new formulations of drug delivery and novel compounds which can interact with fungal virulence are developed and used to treat antifungal infections.

Keywords: Antifungal agents, azoles, Candida albicans, virulence factors, drug resistance, natural product, nanoformulation.

Graphical Abstract

[1]
Ruhnke, M.; Eigler, A.; Tennagen, I.; Geideler, B. Emergence of fluconazole-resistant strains of Candida albicans in patients with recurrent oropharyngeal candidosis and human immunodeficiency virus infection. Clin. Microbiol., 1994, 32, 2092-2098.
[2]
Owotade, F.J.; Shiboski, C.H.; Poole, L.; Ramstead, C.A.; Malvin, K.; Hecht, F.M.; Greenspan, J.S. Prevalence of oral disease among adults with primary HIV infection. Oral Dis., 2008, 14(6), 497-499.
[3]
Mishra, N.N.; Prasad, T.; Sharma, N.; Payasi, A.; Prasad, R.; Gupta, D.K.; Singh, R. Pathogenicity and drug resistance in Candida albicans and other yeast species. Acta Microbiol. Immunol. Hung., 2007, 54, 201-235.
[4]
McNeil, M.M.; Nash, S.L.; Hajjeh, R.A.; Phelan, M.A.; Conn, L.A.; Plikaytis, B.D.; Warnock, D.W. Trends in mortality due to invasive mycotic diseases in the United States, 1980-1997. Clin. Infect. Dis., 2001, 33, 641-647.
[5]
Pierce, C.G.; Lopez-Ribot, J.L. Candidiasis drug discovery and development: new approaches targeting virulence for discovering and identifying new drugs. Expert Opin. Drug Discov., 2013, 8, 1117-1126.
[6]
Fortun, J.; Martín-Dávila, P. Gómez-García, de la Pedrosa E.; Pintado, V.; Cobo, J.; Fresco, G.; Meije, Y.; Ros, L.; Alvarez, ME.; Luengo, J.; Agundez, M.; Belso, A.; Sánchez-Sousa, A.; Loza, E.; Moreno, S. Emerging trends in candidemia: A higher incidence but a similar outcome. J. Infect., 2012, 65, 64-70.
[7]
Yun-Liang, Y.J.; Yin-Zhi, C.; Wen-Li, C.; May-Su, Y.; Hsiu-Jung, L. Zebrafish egg infection model for studying Candida albicans adhesion factors. Microbial. Immunol. Infect, 2003, 36, 223-228.
[8]
Wenzel, R.P. Nosocomial candidemia; Risk factors and prognosis revisited; 11 years experience from a norwegian secondary hospital. Clin. Infect. Dis., 1995, 20, 1531-1534.
[9]
Pfaller, M.A.; Jones, R.N.; Doern, G.V.; Sader, H.S.; Messer, H.A.; Houston, A.; Coffman, S.; Hollis, R.J. Antimicrob. Agents Chemother., 2000, 44, 747-751.
[10]
Retallack, D.M.; Deepe, G.S. Jr.; Woods, J.P. Applying in vivo expression technology (IVET) to the fungal pathogen histoplasma capsulatum. Microb. Pathog., 2000, 28, 169-182.
[11]
Brady, G. Expression profiling of single mammalian cells-small is beautiful. Yeast, 2000, 17, 211-217.
[12]
Hensel, M.; Shea, J.E.; Gleeson, C.; Jones, M.D.; Dalton, E.; Holden, D.W. Simultaneous identification of bacterial virulence genes by negative selection. Science, 1995, 269, 400-403.
[13]
Ghannoum, M.A. Potential role of phospholipases in virulence and fungal pathogenesis. Clin. Microbiol. Rev., 2000, 13, 122-143.
[14]
Monod, M.; Togni, G.; Hube, B.; Sanglard, D. Multiplicity of genes encoding secreted aspartic proteinases in Candida species. Mol. Microbiol., 1994, 13, 357-368.
[15]
Zaugg, C.; Borg-Von, Z.M.; Reichard, U.; Sanglard, D.; Monod, M. Secreted aspartic proteinase family of Candida tropicalis. Infect. Immun., 2001, 69, 405-412.
[16]
Schaller, M.; Hube, B.; Ollert, M.W.; Schafer, W.; Borg-von, M. Zepelin.; E., Thoma-Greber, H.; Korting, C. In vivo expression and localization of Candida albicans secreted aspartyl proteinases during oral candidiasis in HIV-infected patients. J. Invest. Dermatol., 1999, 112, 383-386.
[17]
Slutsky, B.; Staebell, M.; Anderson, J.; Risen, L.; Pfaller, M.; Soll, D.R. “White-opaque transition”: A second high-frequency switching system in Candida albicans. J. Bacteriol., 1987, 169, 5579-5588.
[18]
DeBernardis, F.; Arancia, S.; Morelli, L.; Hube, B.; Sanglard, D.; Schafer, W.; Cassone, A. Evidence that members of the secretory aspartyl proteinase gene family, in particular SAP2, are virulence factors for Candida vaginitis. J. Infect. Dis., 1995, 179, 201-208.
[19]
Pomes, R.; Gil, C.N. Genetic analysis of Candida albicans morphological mutants. J. Gen. Microbiol., 1985, 131, 2107-2113.
[20]
Slutsky, B.; Buffo, J.; Soll, D.R. High frequency switching of colony morphology in Candida albicans. Science, 1985, 230, 666-669.
[21]
Morrow, B.; Srikantha, T.; Anderson, J.; Soll, D.R. Coordinate regulation of two opaque-phase-specific genes during white-opaque switching in Candida albicans. Infect. Immun., 1993, 61, 1823-1828.
[22]
Kvaal, C.; Lachke, S.A.; Srikantha, T.; Daniels, K.; McCoy, J.; Soll, D.R. Misexpression of the opaque-phase-specific gene PEP1 (SAP1) in the white phase of Candida albicans confers increased virulence in a mouse model of cutaneous infection. Infect. Immun., 1999, 67(12), 6652-6662.
[23]
Edmond, M.B.; Wallace, S.E.; McClish, D.K.; Pfaller, M.A.; Jones, R.N.; Wenzel, R.P. Clin. Infect. Dis., 1999, 29, 239-244.
[24]
Nobile, C.J.; Fox, E.P.; Nett, J.E.; Sorrells, T.R.; Mitrovich, Q.M.; Hernday, A.D.; Tuch, B.B.; Andes, D.R.; Johnson, A.D. A recently evolved transcriptional network controls biofilm development in Candida albicans. Cell, 2012, 148, 126-138.
[25]
Gallis, H.A.; Drew, R.H.; Pickard, W.W. Amphotericin B: 30 years of clinical experience. Rev. Infect. Dis., 1990, 12(2), 308-329.
[26]
Dennis, M. Med. Microbiol, 4th ed; Galveston (TX): University of Texas Medical Branch at Galveston, 1996.
[27]
Onyewu, C.; Blankenship, J.R.; Del, P.M.; Heitman, J. Ergosterol biosynthesis inhibitors become fungicidal when combined with calcineurin inhibitors against Candida albicans, Candida glabrata, and Candida krusei. Antimicrob. Agents Chemother., 2003, 47(3), 956-964.
[28]
Nidhi, R.; Ajay, S.; Girish, K.G.; Randhir, S. Imidazoles as Potential Antifungal Agents. Mini Rev. Med. Chem., 2013, 13, 1626-1655.
[29]
Gerald, P.B. Azole antifungal agents. Clin. Infect. Dis., 1992, 14, S161-S169.
[30]
Andes, D. Optimizing antifungal choice and administration. Curr. Med. Res. Opin., 2013, 29, 13-18.
[31]
Lamb, D.; Kelly, D.; Kelly, S. Molecular aspects of azole antifungal action and resistance. Drug Resist. Updat., 1999, 2, 390-402.
[32]
Katiyar, S.K.; Edlind, T.D. Identification and expression of multidrug resistance-related ABC transporter genes in Candida krusei. Med. Mycol., 2001, 39(1), 109-116.
[33]
Becher, R.; Wirsel, S.G. Fungal cytochrome P450 sterol 14α-demethylase (CYP51) and azole resistance in plant and human pathogens. Appl. Microbiol. Biotechnol., 2012, 95(4), 825-840.
[34]
Stana, A.; Dan, C.V.; Radu, T.; Adrian, P.; Laurian, V.; Ioana, I.; Ovidiu, O.; Brînduşa, T. Design, synthesis and antifungal activity evaluation of new thiazolin-4-ones as potential lanosterol 14α-demethylase inhibitors. Int. J. Mol. Sci., 2017, 18(1), 177.
[35]
Abhinandan, P.; Shivaji, P.; John, D. Granules of unistrain lactobacillus as nutraceutical antioxidant agent. Int. J. Pharm. Sci. Res., 2013, 4, 11-13.
[36]
Loeffler, J.; Hermann, E.; Holger, H.; Ulrike, S.; Claudia, H.; Günther, D. Phospholipid and sterol analysis of plasma membranes of azole-resistant Candida albicans strains. FEMS Microbiol. Lett., 2000, 185(1), 59-63.
[37]
Lupetti, A.; Danesi, R.; Campa, M.; Del, T.M.; Kelly, S. Molecular basis of resistance to azole antifungals. Trends Mol. Med., 2002, 8(2), 76-81.
[38]
Lyons, C.N.; White, T.C. Transcriptional analyses of antifungal drug resistance in Candida albicans. Antimicrob. Agents Chemother., 2000, 44(9), 2296-2303.
[39]
Lopez-Ribot, J.L.; McAtee, R.K.; Lee, L.N.; Kirkpatrick, W.R.; White, T.C.; Sanglard, D.; Patterson, T.F. Distinct patterns of gene expression associated with development of fluconazole resistance in serial Candida albicans isolates from human immunodeficiency virus-infected patients with oropharyngeal candidiasis. Antimicrob. Agents Chemother., 1998, 42, 2932-2937.
[40]
Marr, K.A.; Lyons, C.N.; Rustad, T.; Bowden, R.A.; White, T.C. Rapid, transient fluconazole resistance in Candida albicans is associated with increased mRNA levels of CDR. Antimicrob. Agents Chemother., 1998, 42(10), 2584-2589.
[41]
Gupta, A.K.; Simpson, F.C. New therapeutic options for onychomycosis. Expert Opin. Pharmacother., 2012, 13, 1131-1142.
[42]
Perea, S.; Lopez-Ribot, J.L.; Kirkpatrick, W.R.; McAtee, R.K.; Santillan, R.A.; Martinez, M.; Calabrese, D.; Sanglard, D.; Patterson, T.F. Prevalence of molecular mechanisms of resistance to azole antifungal agents in Candida albicans strains displaying high-level fluconazole resistance isolated from human immunodeficiency virus-infected patients. Antimicrob. Agents Chemother., 2001, 45, 2676-2684.
[43]
Fung-Tomc, J.C.; White, T.C.; Minassian, B.; Huczko, E.; Bonner, D.P. In vitro antifungal activity of BMS-207147 and itraconazole against yeast strains that are non-susceptible to fluconazole. Dia. Microbiol. Infect. Dis., 1999, 35, 163-167.
[44]
Sanglard, D.; Ischer, F.; Calabrese, D.; Majcherczyk, P.A.; Bille, J. The ATP binding cassette transporter gene CgCDR1 from Candida glabrata is involved in the resistance of clinical isolates to azole antifungal agents. Antimicrob. Agents Chemother., 1999, 43(11), 2753-2765.
[45]
Marichal, P.; Gorrens, J.; Coene, M.C.; Le Jeune, L.; Vanden Bossche, H. Origin of differences in susceptibility of Candida krusei to azole antifungal agents. Mycoses, 1995, 38, 111-117.
[46]
Katiyar, S.K.; Edlind, T.D. Identification and expression of multidrug resistance-related ABC transporter genes in Candida krusei. Med. Mycol., 2001, 39, 109-116.
[47]
Fidel, P.L.; Vazquez, J.A.; Sobel, J.D. Candida glabrata: Review of epidemiology, pathogenesis, and clinical disease with comparison to C. albicans. Clin. Microbiol. Rev., 1999, 12(1), 80-96.
[48]
Hallstrom, T.C.; Moye-Rowley, W.S. Multiple signals from dysfunctional mitochondria activate the pleiotropic drug resistance pathway in Saccharomyces cerevisiae. J. Biol. Chem., 2000, 275(48), 37347-37356.
[49]
Kenna, S.; Bligh, H.F.J.; Watson, P.F.; Kelly, S.L. Genetic and physiological analysis of azole sensitivity in Saccharomyces cerevisiae. J. Med. Vet. Mycol., 1989, 27, 397-406.
[50]
Traven, A.; Wong, J.M.; Xu, D. Interorganellar communication: Altered nuclear gene expression profiles in a yeast mitochondrial DNA mutant. J. Biol. Chem., 2001, 276, 4020-4027.
[51]
Barchiesi, F.; Calabrese, D.; Sanglard, D.; Luigi, F.D.F.; Caselli, F.; Giannini, D.; Giacometti, A.; Gavaudan, S.; Scalise, G. Experimental induction of fluconazole resistance in Candida tropicalis ATCC 750. Antimicrob. Agents Chemother., 2000, 44(6), 1578-1584.
[52]
Lipinski, C.A.; Lombardo, F.; Dominy, B.W.; Feeney, P.J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev., 2001, 46(1-3), 3-26.
[53]
Cong, F.; Cheung, A.K.; Huang, S.M. Chemical genetics-based target identification in drug discovery. Annu. Rev. Pharmacol. Toxicol., 2012, 52, 57-78.
[54]
Jeffery, D.A.; Bogyo, M. Chemical proteomics and its application to drug discovery. Curr. Opin. Biotechnol., 2003, 14(1), 87-95.
[55]
Spring, D.R. Chemical genetics to chemical genomics: small molecules offer big insights. Chem. Soc. Rev., 2003, 34, 472-482.
[56]
Wang, Y.; Xiao, J.; Suzek, T.O.; Zhang, J.; Wang, J.; Bryant, S.H. PubChem: A public information system for analyzing bioactivities of small molecules. Nucleic Acids Res., 2009, 37, W623-W633.
[57]
Workman, P.; Collins, I. Probing the probes: Fitness factors for small molecule tools. Chem. Biol., 2010, 17(6), 561-577.
[58]
Chen, J.; Swamidass, S.J.; Dou, Y.; Bruand, J.; Baldi, P. Chem. D.B. A public database of small molecules and related chemoinformatics resources. Bioinformatics, 2005, 21, 4133-4139.
[59]
Dobson, C.M. Chemical space and biology. Nature, 2004, 432(7019), 824-828.
[60]
Lipinski, C.; Hopkins, A. Navigating chemical space for biology and medicine. Nature, 2004, 432(7019), 855-861.
[61]
Ohlmeyer, M.; Zhou, M-M. Integration of Small-Molecule Discovery in academic biomedical research. Mt. Sinai J. Med., 2010, 77, 350-357.
[62]
Schreiber, S.L. Target-oriented and diversity-oriented organic synthesis in drug discovery. Science, 2000, 287(5460), 1964-1969.
[63]
Fung-Tomc, J.C.; Bonner, D.P. Recent developments in pradimicin-benanomicin and triazole antibiotics. Exp Opin. Investig. Drugs, 1997, 6, 129-145.
[64]
Yamada, H.T.; Azuma, K. Evaluation of the in vitro antifungal activity of allicin. Antimicrob. Agents Chemother., 1997, 41, 2710-2713.
[65]
Graybill, J.R.; Najvan, L.K.; Holmberg, J.D.; Luther, M.F. Fluconazole, D0870, and flucytosine treatment of disseminated Candida tropicalis infections in mice. Antimicrob. Agents Chemother., 1995, 39, 924-929.
[66]
Fidel, P.L.J.; Cutright, J.L.; Sobel, J.D. Efficacy of D0870 treatment of experimental Candida vaginitis. Antimicrob. Agents Chemother., 1997, 41, 1455-1459.
[67]
Clemons, K.V.; Hanson, L.H.; Stevens, D.A. Activities of the triazole D0870 in vitro and against murine blastomycosis. Antimicrob. Agents Chemother., 1993, 37, 1177-1179.
[68]
Yamada, H.T.; Watanabe, T.; Kato, K.; Mochizuki, H. Fungicidal mechanism of action of D0870 against Cryptococcus neoformans under Acidic Conditions. Antimicrob. Agents Chemother., 1997, 41(12), 2710-2713.
[69]
Bartroli, J.; Turmo, E.; Alguero, M.; Boncompte, E.; Vericat, M.L.; Rafanell, J.G.; Forn, J. Synthesis and antifungal activity of new azole derivatives containing an N-Acylmorpholine ring. J. Med. Chem., 1995, 38, 3918-3932.
[70]
Sheehan, D.J.; Hitchcock, C.A.; Sibley, C.M. Current and emerging azole antifungal agents. Clin. Microbiol. Rev., 1999, 12(1), 40-79.
[71]
Fung-Tomc, J.C.; Huczko, E.; Minassian, B.; Bonner, D.P. In Vitro activity of a new oral triazole, BMS-207147 (ER-30346). Antimicrob. Agents Chemother., 1998, 42(2), 313-318.
[72]
Hata, K.; Ueno, J.; Miki, H.; Toyosawa, T.; Katsu, K.; Nakamura, T.; Horie, T. In: Program and Abstracts of the 35th InterscienceConference on Antimicrobial and Chemotherapy; American society for Microbiology; Washington D. C,, 1995; F92, p. 129.
[73]
Hata, K.; Kimura, J.; Miki, H.; Toyosawa, T.; Nakamura, T.; Katsu, K. In vitro and in vivo antifungal activities of ER-30346, a novel oral triazole with a broad antifungal spectrum. Antimicrob. Agents Chemother., 1996, 40, 2237-2242.
[74]
Hitchcock, C.A. Program and Abstracts of the 35th Interscience conference on antimicrobial agents and chemotherapy; american society for microbiology, 1995, F 72, p. 125.
[75]
Barry, A.L.; Brown, S.D. In vitro studies of two triazole antifungal agents (voriconazole [UK-109,496] and fluconazole) against Candida species. Antimicrob. Agents Chemother., 1996, 40, 1948-1949.
[76]
Rhunke, M.; Schmidt-Westhausen, A.; Trautmann, M. In vitro activities of voriconazole (UK-109,496) against fluconazole-susceptible and resistant Candida albicans isolates from oral cavities of patients with human immunodeficiency virus infection. Antimicrob. Agents Chemother., 1997, 41, 575-577.
[77]
Pfaller, M.A.; Castanheira, M.; Diekema, D.J.; Messer, S.A.; Moet, G.J.; Jones, R.N. Comparison of european committee on antimicrobial susceptibility testing (EUCAST) and etest methods with the clsi broth microdilution method for echinocandin susceptibility testing of candida species. J. Clin. Microbiol., 2010, 48(5), 1592-1599.
[78]
Cuenca-Estrella, M.; Rodriguez-Tudela, J.L. The current role of the reference procedures by CLSI and EUCAST in the detection of resistance to antifungal agents in vitro. Expert Rev. Anti Infect. Ther., 2010, 8, 267-276.
[79]
Alex, D.; Gay-Andrieu, F.; May, J.; Thampi, L.; Dou, D.; Mooney, A.; Groutas, W.; Calderone, R. Amino Acid-Derived 1,2-Benzisothiazolinone Derivatives as Novel Small-Molecule Antifungal Inhibitors: Identification of Potential Genetic Targets. Antimicrob. Agents Chemother., 2012, 56(9), 4630-4639.
[80]
Dou, D.; Alex, D.; Du, B.; Tiew, K.C.; Aravapalli, S.; Mandadapu, S.R.; Calderone, R.; Groutas, W.C. Antifungal activity of a series of 1,2-benzisothiazol-3(2H)-one derivatives. Bioorg. Med. Chem., 2011, 19(19), 5782-5787.
[81]
Bardiot, D.; Thevissen, K.; De Brucker, K.; Peeters, A.; Cos, P.; Taborda, C.; McNaughton, M.; Maes, L.; Chaltin, P.; Cammue, B.P.A.; Marchand, A. 2-(2-Oxo-morpholin-3-yl)-acetamide Derivatives as Broad-Spectrum Antifungal Agents. J. Med. Chem., 2015, 58, 1502-1512.
[82]
Law, D.; Moore, C.B.; Denning, D.W. Activity of SCH 56592 compared with those of fluconazole and itraconazole against Candida spp. Antimicrob. Agents Chemother., 1997, 41(10), 2310-2311.
[83]
Pfaller, M.A.; Messer, S.; Jones, R.N. Activity of a new triazole, Sch 56592, compared with those of four other antifungal agents tested against clinical isolates of Candida spp. and Saccharomyces cerevisiae. Antimicrob. Agents Chemother., 1997, 41, 233-235.
[84]
Perfect, J.R.; Cox, G.M.; Dodge, R.K. Schell. W.A. In vitro and in vivo efficacies of the azole SCH56592 against Cryptococcus neoformans. Antimicrob. Agents Chemother., 1996, 40, 1910-1913.
[85]
Newman, D.J.; Cragg, G.M.; Snader, K.M. The influence of natural products upon drug discovery. Nat. Prod. Rep., 2000, 17, 215-234.
[86]
Sneader, W. Drug Prototypes and their Exploitation; Wiley: Chichester, 1996.
[87]
Buss, A.D. Burger’s Medicinal Chemistry and Drug Discovery6th Ed. Drug Discovery; ed. Abraham, D. J.; Wiley: New Jersey, 2003, 1, pp. 847-900.
[88]
Calderone, R.A.. Fonzi, W.A. Virulence factor of Candida albicans. Trends Microbiol., 2001, 9(7), 327-335.