Login Register Cart 0
Generic placeholder image

Current Topics in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

The Chemistry of Drugs to Treat Candida albicans

Author(s): Aurelio Ortiz and Estibaliz Sansinenea*

Volume 19, Issue 28, 2019

Page: [2554 - 2566] Pages: 13

DOI: 10.2174/1568026619666191025153124

Price: $65

Abstract

Background: Candida species are in various parts of the human body as commensals. However, they can cause local mucosal infections and, sometimes, systemic infections in which Candida species can spread to all major organs and colonize them.

Objective: For the effective treatment of the mucosal infections and systemic life-threatening fungal diseases, a considerably large number of antifungal drugs have been developed and used for clinical purposes that comprise agents from four main drug classes: the polyenes, azoles, echinocandins, and antimetabolites.

Methods: The synthesis of some of these drugs is available, allowing synthetic modification of the molecules to improve the biological activity against Candida species. The synthetic methodology for each compound is reviewed.

Results: The use of these compounds has caused a high-level resistance against these drugs, and therefore, new antifungal substances have been described in the last years. The organic synthesis of the known and new compounds is reported.

Conclusion: This article summarizes the chemistry of the existing agents, both the old drugs and new drugs, in the treatment of infections due to C. albicans, including the synthesis of the existing drugs.

Keywords: Candida albicans, Candida krusei, Antifungals, anti-Candida compounds, Candidiasis, Fungal infections.

« Previous Next »
Graphical Abstract

[1]
Kathiravan, M.K.; Salake, A.B.; Chothe, A.S.; Dudhe, P.B.; Watode, R.P.; Mukta, M.S.; Gadhwe, S. The biology and chemistry of antifungal agents: a review. Bioorg. Med. Chem., 2012, 20(19), 5678-5698.
[http://dx.doi.org/10.1016/j.bmc.2012.04.045] [PMID: 22902032]
[2]
Kabir, M.A.; Ahmad, Z. Candida infections and their prevention. ISRN Prev. Med., 2013, 2013, 1-13.
[http://dx.doi.org/ 10.5402/2013/763628]
[3]
Srivastava, V.; Singla, R.K.; Dubey, A.K. Emerging virulence, drug resistance and future anti-fungal drugs for candida pathogens. Curr. Top. Med. Chem., 2018, 18(9), 759-778.
[http://dx.doi.org/10.2174/1568026618666180528121707] [PMID: 29807516]
[4]
Moudgal, V.; Sobel, J. Antifungals to treat Candida albicans. Expert Opin. Pharmacother., 2010, 11(12), 2037-2048.
[http://dx.doi.org/10.1517/14656566.2010.493875] [PMID: 20536294]
[5]
Campoy, S.; Adrio, J.L. Antifungals. Biochem. Pharmacol., 2017, 133, 86-96.
[http://dx.doi.org/10.1016/j.bcp.2016.11.019] [PMID: 27884742]
[6]
Zida, A.; Bamba, S.; Yacouba, A.; Ouedraogo-Traore, R.; Guiguemdé, R.T. Anti-Candida albicans natural products, sources of new antifungal drugs: A review. J. Mycol. Med., 2017, 27(1), 1-19.
[http://dx.doi.org/10.1016/j.mycmed.2016.10.002] [PMID: 27842800]
[7]
Lemke, A.; Kiderlen, A.F.; Kayser, O.; Amphotericin, B.; Amphotericin, B. Appl. Microbiol. Biotechnol., 2005, 68(2), 151-162.
[http://dx.doi.org/10.1007/s00253-005-1955-9] [PMID: 15821914]
[8]
Volmer, A.A.; Szpilman, A.M.; Carreira, E.M. Synthesis and biological evaluation of amphotericin B derivatives. Nat. Prod. Rep., 2010, 27(9), 1329-1349.
[http://dx.doi.org/10.1039/b820743g] [PMID: 20556271]
[9]
Bonini, C.; Giugliano, A.; Racioppi, R.; Righi, G. Synthesis of the Ci-C~0 fragment of the macrolide antibiotic nystatin al from a chiral building block obtained via chemoenzymatic approach. Tetrahedron Lett., 1996, 37, 2487.
[http://dx.doi.org/10.1016/0040-4039(96)00300-0]
[10]
Schneider, C.; Rehfeuter, M. Enantioselective polyol synthesis via the cope rearrangement of chiral aldol products. A synthesis of the Cl-CIO-fragment of nystatin Al. Tetrahedron Lett., 1998, 39, 9.
[http://dx.doi.org/10.1016/S0040-4039(97)10455-5]
[11]
Solladié, G.; Wilb, N.; Bauder, C.; Bonini, C.; Viggiani, L.; Chiummiento, L. First stereocontrolled synthesis of the (3S,5R,7R,10R,11R)-C1-C13 fragment of nystatin A(1). J. Org. Chem., 1999, 64(15), 5447-5452.
[http://dx.doi.org/10.1021/jo990245y] [PMID: 11674606]
[12]
Kadota, I.; Hu, Y.; Packard, G.K.; Rychnovsky, S.D. A unified approach to polyene macrolides: synthesis of candidin and nystatin polyols. Proc. Natl. Acad. Sci. USA, 2004, 101(33), 11992-11995.
[http://dx.doi.org/10.1073/pnas.0401552101] [PMID: 15192147]
[13]
Maertens, J.A. History of the development of azole derivatives. Clin. Microbiol. Infect., 2004, 10(Suppl. 1), 1-10.
[http://dx.doi.org/10.1111/j.1470-9465.2004.00841.x] [PMID: 14748798]
[14]
Mast, N.; Zheng, W.; Stout, C.D.; Pikuleva, I.A. Antifungal azoles: structural insights into undesired tight binding to cholesterol metabolizing CYP46A1. Mol. Pharmacol., 2013, 84(1), 86-94.
[http://dx.doi.org/10.1124/mol.113.085902] [PMID: 23604141]
[15]
Peyton, L.R.; Gallagher, S.; Hashemzadeh, M. Triazole antifungals: a review. Drugs Today (Barc), 2015, 51(12), 705-718.
[http://dx.doi.org/ 10.1358/dot.2015.51.12.2421058] [PMID: 26798851]
[16]
Fothergill, A.W. Miconazole: A historical perspective. Expert Rev. Anti Infect. Ther., 2006, 4(2), 171-175.
[http://dx.doi.org/10.1586/14787210.4.2.171] [PMID: 16597199]
[17]
Cuevas Yanez, E. Canul sanchez, A.; Serrano Becerra, J.M.; Muchowski, J.M.; Cruz Almanza, R. Synthesis of miconazole and analogs through a carbenoid intermediate. Rev. Soc. Quím. Méx., 2004, 48, 49-52.
[18]
Mangas-Sánchez, J.; Busto, E.; Gotor-Fernández, V.; Malpartida, F.; Gotor, V. Asymmetric chemoenzymatic synthesis of miconazole and econazole enantiomers. The importance of chirality in their biological evaluation. J. Org. Chem., 2011, 76(7), 2115-2122.
[http://dx.doi.org/10.1021/jo102459w] [PMID: 21384803]
[19]
Zervos, M.; Meunier, F. Fluconazole (Diflucan): A review. Int. J. Antimicrob. Agents, 1993, 3(3), 147-170.
[http://dx.doi.org/10.1016/0924-8579(93)90009-T] [PMID: 18611557]
[20]
Tamura, K.; Kumagai, N.; Shibasaki, M. An enantioselective synthesis of the key intermediate for triazole antifungal agents; application to the catalytic asymmetric synthesis of efinaconazole (Jublia). J. Org. Chem., 2014, 79(7), 3272-3278.
[http://dx.doi.org/10.1021/jo500369y] [PMID: 24635354]
[21]
Letscher-Bru, V.; Herbrecht, R. Caspofungin: The first representative of a new antifungal class. J. Antimicrob. Chemother., 2003, 51(3), 513-521.
[http://dx.doi.org/10.1093/jac/dkg117] [PMID: 12615851]
[22]
Hashimoto, S. Micafungin: a sulfated echinocandin. J. Antibiot. (Tokyo), 2009, 62(1), 27-35.
[http://dx.doi.org/10.1038/ja.2008.3] [PMID: 19132058]
[23]
Abonia, R.; Garay, A.; Castillo, J.C.; Insuasty, B.; Quiroga, J.; Nogueras, M.; Cobo, J.; Butassi, E.; Zacchino, S. Design of two alternative routes for the synthesis of naftifine and analogues as potential antifungal agents. Molecules, 2018, 23(3), 520.
[http://dx.doi.org/10.3390/molecules23030520] [PMID: 29495412]
[24]
Stütz, A.; Georgopoulos, A.; Granitzer, W.; Petranyi, G.; Berney, D. Synthesis and structure-activity relationships of naftifine-related allylamine antimycotics. J. Med. Chem., 1986, 29(1), 112-125.
[http://dx.doi.org/10.1021/jm00151a019] [PMID: 3510297]
[25]
Petasis, N.A.; Akritopoulou, I. The boronic acid Mannich reaction: A new method for the synthesis of geometrically pure allylamines. Tetrahedron Lett., 1993, 34, 583-586.
[http://dx.doi.org/10.1016/S0040-4039(00)61625-8]
[26]
Prediger, P.; Barbosa, L.F.; Génisson, Y.; Correia, C.R. Substrate-directable Heck reactions with arenediazonium salts. The regio- and stereoselective arylation of allylamine derivatives and applications in the synthesis of naftifine and abamines. J. Org. Chem., 2011, 76(19), 7737-7749.
[http://dx.doi.org/10.1021/jo201105z] [PMID: 21877731]
[27]
Alami, M.; Ferri, F.; Gaslain, Y. A Two-step synthesis of terbinafine. Tetrahedron Lett., 1996, 37, 57-58.
[http://dx.doi.org/10.1016/0040-4039(95)02095-0]
[28]
Vermes, A.; Guchelaar, H.J.; Dankert, J. Flucytosine: a review of its pharmacology, clinical indications, pharmacokinetics, toxicity and drug interactions. J. Antimicrob. Chemother., 2000, 46(2), 171-179.
[http://dx.doi.org/10.1093/jac/46.2.171] [PMID: 10933638]
[29]
Harsanyi, A.; Conte, A.; Pichon, L.; Rabion, A.; Grenier, S.; Sandford, G. One-step continuous flow synthesis of antifungal WHO essential medicine flucytosine using fluorine. Org. Process Res. Dev., 2017, 21, 273-276.
[http://dx.doi.org/10.1021/acs.oprd.6b00420]
[30]
Paquet, V.; Carreira, E.M. Significant improvement of antifungal activity of polyene macrolides by bisalkylation of the mycosamine. Org. Lett., 2006, 8(9), 1807-1809.
[http://dx.doi.org/10.1021/ol060353o] [PMID: 16623556]
[31]
Ramírez-Villalva, A.; González-Calderón, D.; González-Romero, C.; Morales-Rodríguez, M.; Jauregui-Rodríguez, B.; Cuevas-Yáñez, E.; Fuentes-Benítes, A. A facile synthesis of novel miconazole analogues and the evaluation of their antifungal activity. Eur. J. Med. Chem., 2015, 97, 275-279.
[http://dx.doi.org/10.1016/j.ejmech.2015.04.047] [PMID: 25989345]
[32]
Pore, V.S.; Agalave, S.G.; Singh, P.; Shukla, P.K.; Kumar, V.; Siddiqi, M.I. Design and synthesis of new fluconazole analogues. Org. Biomol. Chem., 2015, 13(23), 6551-6561.
[http://dx.doi.org/10.1039/C5OB00590F] [PMID: 25975803]
[33]
Bartroli, J.; Turmo, E.; Algueró, M.; Boncompte, E.; Vericat, M.L.; Conte, L.; Ramis, J.; Merlos, M.; García-Rafanell, J.; Forn, J. New azole antifungals. 3. Synthesis and antifungal activity of 3-substituted-4(3H)-quinazolinones. J. Med. Chem., 1998, 41(11), 1869-1882.
[http://dx.doi.org/10.1021/jm9707277] [PMID: 9599237]
[34]
Guillon, R.; Pagniez, F.; Picot, C.; Hédou, D.; Tonnerre, A.; Chosson, E.; Duflos, M.; Besson, T.; Logé, C.; Le Pape, P. Discovery of a novel broad-spectrum antifungal agent derived from albaconazole. ACS Med. Chem. Lett., 2013, 4(2), 288-292.
[http://dx.doi.org/10.1021/ml300429p] [PMID: 24900660]
[35]
Oliveira, A.S.; Gaspar, C.A.; Palmeira-de-Oliveira, R.; Martinez-de-Oliveira, J.; Palmeira-de-Oliveira, A. Anti-Candida activity of fluoxetine alone and combined with fluconazole: a synergistic action against fluconazole-resistant strains. Antimicrob. Agents Chemother., 2014, 58(7), 4224-4226.
[http://dx.doi.org/10.1128/AAC.02623-13] [PMID: 24798281]
[36]
Silvestri, R.; Artico, M.; La Regina, G.; Di Pasquali, A.; De Martino, G.; D’Auria, F.D.; Nencioni, L.; Palamara, A.T. Imidazole analogues of fluoxetine, a novel class of anti-Candida agents. J. Med. Chem., 2004, 47(16), 3924-3926.
[http://dx.doi.org/10.1021/jm049856v] [PMID: 15267229]
[37]
Božinović, N.; Šegan, S.; Vojnovic, S.; Pavic, A.; Šolaja, B.A.; Nikodinovic-Runic, J.; Opsenica, I.M. Synthesis and anti-Candida activity of novel benzothiepino[3,2-c]pyridine derivatives. Chem. Biol. Drug Des., 2016, 88(6), 795-806.
[http://dx.doi.org/10.1111/cbdd.12809] [PMID: 27316378]
[38]
Radwan, A.A.; Alanazi, F.K.; Al-Agamy, M.H. 1,3,4-Thiadiazole and 1,2,4-triazole-3(4H)-thione bearing salicylate moiety: synthesis and evaluation as anti-Candida albicans. Braz. J. Pharm. Sci., 2017, 53e15239
[http://dx.doi.org/10.1590/s2175-97902017000115239]
[39]
Abonia, R.; Garay, A.; Castillo, J.C.; Insuasty, B.; Quiroga, J.; Nogueras, M.; Cobo, J.; Butassi, E.; Zacchino, S. Design of two alternative routes for the synthesis of naftifine and analogues as potential antifungal agents. Molecules, 2018, 23(3), 520.
[http://dx.doi.org/10.3390/molecules23030520] [PMID: 29495412]
[40]
Thibane, V.S.; Kock, J.L.F.; Van Wyk, P.W.J.; Ells, R.; Pohl, C.H. Stearidonic acid acts in synergism with amphotericin B in inhibiting Candida albicans and Candida dubliniensis biofilms in vitro. Int. J. Antimicrob. Agents, 2012, 40(3), 284-285.
[http://dx.doi.org/10.1016/j.ijantimicag.2012.05.021] [PMID: 22817915]
[41]
Cui, J.; Ren, B.; Tong, Y.; Dai, H.; Zhang, L. Synergistic combinations of antifungals and anti-virulence agents to fight against Candida albicans. Virulence, 2015, 6(4), 362-371.
[http://dx.doi.org/10.1080/21505594.2015.1039885] [PMID: 26048362]
[42]
Zida, A.; Bamba, S.; Yacouba, A.; Ouedraogo-Traore, R.; Guiguemdé, R.T. Anti-Candida albicans natural products, sources of new antifungal drugs: A review. J. Mycol. Med., 2017, 27(1), 1-19.
[http://dx.doi.org/10.1016/j.mycmed.2016.10.002] [PMID: 27842800]
[43]
Hwang, J.H.; Jin, Q.; Woo, E-R.; Lee, D.G. Antifungal property of hibicuslide C and its membrane-active mechanism in Candida albicans. Biochimie, 2013, 95(10), 1917-1922.
[http://dx.doi.org/10.1016/j.biochi.2013.06.019] [PMID: 23816874]
[44]
Hwang, J.H.; Choi, H.; Kim, A.R.; Yun, J.W.; Yu, R.; Woo, E-R.; Lee, D.G. Hibicuslide C-induced cell death in Candida albicans involves apoptosis mechanism. J. Appl. Microbiol., 2014, 117(5), 1400-1411.
[http://dx.doi.org/10.1111/jam.12633] [PMID: 25176011]
[45]
Gorman, J.A.; Chang, L.P.; Clark, J.; Gustavson, D.R.; Lam, K.S.; Mamber, S.W.; Pirnik, D.; Ricca, C.; Fernandes, P.B.; O’Sullivan, J. Ascosteroside, a new antifungal agent from Ascotricha amphitricha. I. Taxonomy, fermentation and biological activities. J. Antibiot. (Tokyo), 1996, 49(6), 547-552.
[http://dx.doi.org/10.7164/antibiotics.49.547] [PMID: 8698637]
[46]
Harris, G.H.; Shafiee, A.; Cabello, M.A.; Curotto, J.E.; Genilloud, O.; Göklen, K.E.; Kurtz, M.B.; Rosenbach, M.; Salmon, P.M.; Thornton, R.A.; Zink, D.L.; Mandala, S.M. Inhibition of fungal sphingolipid biosynthesis by rustmicin, galbonolide B and their new 21-hydroxy analogs. J. Antibiot. (Tokyo), 1998, 51(9), 837-844.
[http://dx.doi.org/10.7164/antibiotics.51.837] [PMID: 9820234]
[47]
Parsons, P.J.; Pennicott, L.; Eshelby, J.; Goessman, M.; Highton, A.; Hitchcock, P. A total synthesis of galbonolide B. J. Org. Chem., 2007, 72(24), 9387-9390.
[http://dx.doi.org/10.1021/jo701509r] [PMID: 17958371]
[48]
Nirma, C.; Eparvier, V.; Stien, D. Antifungal agents from Pseudallescheria boydii SNB-CN73 isolated from a Nasutitermes sp. termite. J. Nat. Prod., 2013, 76(5), 988-991.
[http://dx.doi.org/10.1021/np4001703] [PMID: 23627396]
[49]
Tae, H.S.; Hines, J.; Schneekloth, A.R.; Crews, C.M. Total synthesis and biological evaluation of tyroscherin. Org. Lett., 2010, 12(19), 4308-4311.
[http://dx.doi.org/10.1021/ol101801u] [PMID: 20831175]
[50]
Hwang, B.; Lee, J.; Liu, Q.H.; Woo, E.R.; Lee, D.G. Antifungal effect of (+)-pinoresinol isolated from Sambucus williamsii. Molecules, 2010, 15(5), 3507-3516.
[http://dx.doi.org/10.3390/molecules15053507] [PMID: 20657496]
[51]
Lee, J.; Hwang, J-S.; Hwang, B.; Kim, J-K.; Kim, S.R.; Kim, Y.; Lee, D.G. Membrane perturbation induced by papiliocin peptide, derived from Papilio xuthus, in Candida albicans. J. Microbiol. Biotechnol., 2010, 20(8), 1185-1188.
[http://dx.doi.org/10.4014/jmb.1004.04014] [PMID: 20798579]
[52]
Conlon, J.M.; Meetani, M.A.; Coquet, L.; Jouenne, T.; Leprince, J.; Vaudry, H.; Kolodziejek, J.; Nowotny, N.; King, J.D. Antimicrobial peptides from the skin secretions of the New World frogs Lithobates capito and Lithobates warszewitschii (Ranidae). Peptides, 2009, 30(10), 1775-1781.
[http://dx.doi.org/10.1016/j.peptides.2009.07.011] [PMID: 19635516]
[53]
Tian, J.; Shen, Y.; Yang, X.; Liang, S.; Shan, L.; Li, H.; Liu, R.; Zhang, W. Antifungal cyclic peptides from Psammosilene tunicoides. J. Nat. Prod., 2010, 73(12), 1987-1992.
[http://dx.doi.org/10.1021/np100363a] [PMID: 21070025]

Rights & Permissions Print Cite
Article Metrics
61
2
© 2024 Bentham Science Publishers | Privacy Policy