1,2,4-Triazole: A Privileged Scaffold for the Development of Potent Antifungal Agents - A Brief Review

Author(s): Christophe Tratrat*

Journal Name: Current Topics in Medicinal Chemistry

Volume 20 , Issue 24 , 2020


Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Abstract:

Over the past decades, a tremendous rise in invasive fungal infection diseases attributed to the yeast Candida albicans in immunocompromised individuals poses a seriously challenging issue. Another concern is the emergence of multi-drug resistant pathogens to the existing medicines due to their overuse and misuse. It was recently reported that 25-55% of the mortality rate is caused by invasive infection. Despite a large variety of drugs being available to treat invasive candidiasis, only two of them contain a 1,2,4-triazole core, namely Fluconazole and itraconazole, which are efficient in treating infection induced by fungal Candida species. Moreover, long-term therapy associated with azole medications has led to an increase in azole resistance as well as a high risk of toxicity. Despite numerous outstanding achievements in antifungal drug discovery, development of novel, safer and potent antifungal agents while overcoming the resistance problem associated with the current drugs is becoming the main focus of medicinal chemists. Therefore, this review outlines the breakthroughs in medicinal chemistry research regarding 1,2,4- triazole-based derivatives as potential antifungal agents in the past decade. In addition, the structureactivity relationship of these compounds is also discussed.

Keywords: Triazole, Fungal infection, Candidiasis, Drug-resistant, Antifungal, Structure-activity relationship.

[1]
Lee, H.; Lee, D.G. Novel approaches for efficient antifungal drug action. J. Microbiol. Biotechnol., 2018, 28(11), 1771-1781.
[http://dx.doi.org/10.4014/jmb.1807.07002 ] [PMID: 30178649]
[2]
Ablordeppey, S.Y.; Fan, P.; Ablordeppey, J.H.; Mardenborough, L. Systemic antifungal agents against AIDS-related opportunistic infections: current status and emerging drugs in development. Curr. Med. Chem., 1999, 6(12), 1151-1195.
[PMID: 10519919]
[3]
Girmenia, C.; Finolezzi, E. New-generation triazole antifungal drugs: Review of the Phase II and III trials. Clin. Investig. (Lond.), 2011, 1, 1577-1594.
[http://dx.doi.org/10.4155/cli.11.137]
[4]
Singh, N. Trends in the epidemiology of opportunistic fungal infections: predisposing factors and the impact of antimicrobial use practices. Clin. Infect. Dis., 2001, 33(10), 1692-1696.
[http://dx.doi.org/10.1086/323895 ] [PMID: 11641825]
[5]
Fridkin, S.K.; Jarvis, W.R. Epidemiology of nosocomial fungal infections. Clin. Microbiol. Rev., 1996, 9(4), 499-511.
[http://dx.doi.org/10.1128/CMR.9.4.499 ] [PMID: 8894349]
[6]
Hokken, M.W.J.; Zwaan, B.J.; Melchers, W.J.G.; Verweij, P.E. Facilitators of adaptation and antifungal resistance mechanisms in clinically relevant fungi. Fungal Genet. Biol., 2019, 132, 103254.
[http://dx.doi.org/10.1016/j.fgb.2019.103254 ] [PMID: 31326470]
[7]
Bongomin, F.; Gago, S.; Oladele, R.O.; Denning, D.W. Global and multi-national prevalence of fungal diseases-estimate precision. J. Fungi (Basel), 2017, 3(4), E57.
[http://dx.doi.org/10.3390/jof3040057 ] [PMID: 29371573]
[8]
Zhao, L.; Tian, L.; Sun, N.; Sun, Y.; Chen, Y.; Wang, X.; Zhao, S.; Su, X.; Zhao, D.; Cheng, M. Design, synthesis, and structure-activity relationship studies of l-amino alcohol derivatives as broad-spectrum antifungal agents. Eur. J. Med. Chem., 2019, 177, 374-385.
[http://dx.doi.org/10.1016/j.ejmech.2019.05.047 ] [PMID: 31158751]
[9]
Peyton, L.R.; Gallagher, S.; Hashemzadeh, M. Triazole antifungals: a review. Drugs Today (Barc), 2015, 51(12), 705-718.
[PMID: 26798851]
[10]
Scorzoni, L.; de Paula, E. Silva, A.C.; Marcos, C.M.; Assato, P.A.; de Melo, W.C.; de Oliveira, H.C.; Costa-Orlandi, C.B.; Mendes-Giannini, M.J.; Fusco-Almeida, A.M. Antifungal therapy: new advances in the understanding and treatment of mycosis. Front. Microbiol., 2017, 8, 36-36.
[http://dx.doi.org/10.3389/fmicb.2017.00036 ] [PMID: 28167935]
[11]
Cowen, L.E.; Sanglard, D.; Howard, S.J.; Rogers, P.D.; Perlin, D.S. Mechanisms of antifungal drug resistance. Cold Spring Harb. Perspect. Med., 2014, 5(7), a019752-a019752.
[http://dx.doi.org/10.1101/cshperspect.a019752 ] [PMID: 25384768]
[12]
Arikan, S.; Rex, J.H. Nystatin LF (Aronex/Abbott). Current opinion in investigational drugs (London, England : 2000), 2001, 2(4), 488-495.
[13]
Denning, D.W. Echinocandin antifungal drugs. Lancet, 2003, 362(9390), 1142-1151.
[http://dx.doi.org/10.1016/S0140-6736(03)14472-8 ] [PMID: 14550704]
[14]
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]
[15]
Allen, D.; Wilson, D.; Drew, R.; Perfect, J. Azole antifungals: 35 years of invasive fungal infection management. Expert Rev. Anti Infect. Ther., 2015, 13(6), 787-798.
[http://dx.doi.org/10.1586/14787210.2015.1032939 ] [PMID: 25843556]
[16]
Herbrecht, R.; Natarajan-Amé, S.; Nivoix, Y.; Letscher-Bru, V. The lipid formulations of amphotericin B. Expert Opin. Pharmacother., 2003, 4(8), 1277-1287.
[http://dx.doi.org/10.1517/14656566.4.8.1277 ] [PMID: 12877636]
[17]
Laniado-Laborín, R.; Cabrales-Vargas, M.N. Amphotericin B: side effects and toxicity. Rev. Iberoam. Micol., 2009, 26(4), 223-227.
[http://dx.doi.org/10.1016/j.riam.2009.06.003 ] [PMID: 19836985]
[18]
Lepesheva, G.I.; Waterman, M.R. Sterol 14alpha-demethylase cytochrome P450 (CYP51), a P450 in all biological kingdoms. Biochim. Biophys. Acta, 2007, 1770(3), 467-477.
[http://dx.doi.org/10.1016/j.bbagen.2006.07.018 ] [PMID: 16963187]
[19]
Di Mambro, T.; Guerriero, I.; Aurisicchio, L.; Magnani, M.; Marra, E. The yin and yang of current antifungal therapeutic strategies: how can we harness our natural defenses? Front. Pharmacol., 2019, 10, 80-80.
[http://dx.doi.org/10.3389/fphar.2019.00080 ] [PMID: 30804788]
[20]
Perfect, J.R. The antifungal pipeline: a reality check. Nat. Rev. Drug Discov., 2017, 16(9), 603-616.
[http://dx.doi.org/10.1038/nrd.2017.46 ] [PMID: 28496146]
[21]
Zhang, J.; Li, L.; Lv, Q.; Yan, L.; Wang, Y.; Jiang, Y. The fungal CYP51S: their functions, structures, related drug resistance, and inhibitors. Front. Microbiol., 2019, 10, 691-691.
[http://dx.doi.org/10.3389/fmicb.2019.00691 ] [PMID: 31068906]
[22]
Barrett-Bee, K.; Newboult, L.; Pinder, P. Biochemical changes associated with the antifungal action of the triazole ICI 153,066 on Candida albicans and Trichophyton quinckeanum. FEMS Microbiol. Lett., 1991, 63(2-3), 127-131.
[http://dx.doi.org/10.1111/j.1574-6968.1991.tb04517.x ] [PMID: 2060756]
[23]
Kaur, P.; Chawla, A. 1,2,4-triazole: A review of pharmacological activities. Intl. Res. J. Pharm., 2017, 8, 10-29.
[http://dx.doi.org/10.7897/2230-8407.087112]
[24]
Martin, M.V. The use of fluconazole and itraconazole in the treatment of Candida albicans infections: a review. J. Antimicrob. Chemother., 1999, 44(4), 429-437.
[http://dx.doi.org/10.1093/jac/44.4.429 ] [PMID: 10588302]
[25]
Chen, A.; Sobel, J.D. Emerging azole antifungals. Expert Opin. Emerg. Drugs, 2005, 10(1), 21-33.
[http://dx.doi.org/10.1517/14728214.10.1.21 ] [PMID: 15757401]
[26]
Benitez, L.L.; Carver, P.L. Adverse effects associated with long-term administration of azole antifungal agents. Drugs, 2019, 79(8), 833-853.
[http://dx.doi.org/10.1007/s40265-019-01127-8 ] [PMID: 31093949]
[27]
Roemer, T.; Krysan, D.J. Antifungal drug development: challenges, unmet clinical needs, and new approaches. Cold Spring Harb. Perspect. Med., 2014, 4(5), a019703.
[http://dx.doi.org/10.1101/cshperspect.a019703 ] [PMID: 24789878]
[28]
Wang, T.; Shao, J.; Da, W.; Li, Q.; Shi, G.; Wu, D.; Wang, C. Strong synergism of palmatine and fluconazole/itraconazole against planktonic and biofilm cells of candida species and efflux-associated antifungal mechanism. Front. Microbiol., 2018, 9, 2892-2892.
[http://dx.doi.org/10.3389/fmicb.2018.02892 ] [PMID: 30559726]
[29]
Gupta, D.; Jain, D.K. Synthesis, antifungal and antibacterial activity of novel 1,2,4-triazole derivatives. J. Adv. Pharm. Technol. Res., 2015, 6(3), 141-146.
[http://dx.doi.org/10.4103/2231-4040.161515 ] [PMID: 26317080]
[30]
Andes, D.; Azie, N.; Yang, H.; Harrington, R.; Kelley, C.; Tan, R-D.; Wu, E.Q.; Franks, B.; Kristy, R.; Lee, E.; Khandelwal, N.; Spalding, J. Drug-drug interaction associated with mold-active triazoles among hospitalized patients. Antimicrob. Agents Chemother., 2016, 60(6), 3398-3406.
[http://dx.doi.org/10.1128/AAC.00054-16 ] [PMID: 27001815]
[31]
Trösken, E.R.; Adamska, M.; Arand, M.; Zarn, J.A.; Patten, C.; Völkel, W.; Lutz, W.K. Comparison of lanosterol-14 alpha-demethylase (CYP51) of human and Candida albicans for inhibition by different antifungal azoles. Toxicology, 2006, 228(1), 24-32.
[http://dx.doi.org/10.1016/j.tox.2006.08.007 ] [PMID: 16989930]
[32]
Cortés, J.C.G.; Curto, M.Á.; Carvalho, V.S.D.; Pérez, P.; Ribas, J.C. The fungal cell wall as a target for the development of new antifungal therapies. Biotechnol. Adv., 2019, 37(6), 107352.
[http://dx.doi.org/10.1016/j.biotechadv.2019.02.008 ] [PMID: 30797093]
[33]
Geronikaki, A.; Fesatidou, M.; Kartsev, V.; Macaev, F. Synthesis and biological evaluation of potent antifungal agents. Curr. Top. Med. Chem., 2013, 13(21), 2684-2733.
[http://dx.doi.org/10.2174/15680266113136660195 ] [PMID: 24083791]
[34]
Nami, S.; Aghebati-Maleki, A.; Morovati, H.; Aghebati-Maleki, L. Current antifungal drugs and immunotherapeutic approaches as promising strategies to treatment of fungal diseases. Biomed. Pharmacother., 2019, 110, 857-868.
[http://dx.doi.org/10.1016/j.biopha.2018.12.009 ] [PMID: 30557835]
[35]
Matsumoto, M.; Ishida, K.; Konagai, A.; Maebashi, K.; Asaoka, T. Strong antifungal activity of SS750, a new triazole derivative, is based on its selective binding affinity to cytochrome P450 of fungi. Antimicrob. Agents Chemother., 2002, 46(2), 308-314.
[http://dx.doi.org/10.1128/AAC.46.2.308-314.2002 ] [PMID: 11796335]
[36]
Cuenca-Estrella, M.; Lee-Yang, W.; Ciblak, M.A.; Arthington-Skaggs, B.A.; Mellado, E.; Warnock, D.W.; Rodriguez-Tudela, J.L. Comparative evaluation of NCCLS M27-A and EUCAST broth microdilution procedures for antifungal susceptibility testing of candida species. Antimicrob. Agents Chemother., 2002, 46(11), 3644-3647.
[http://dx.doi.org/10.1128/AAC.46.11.3644-3647.2002 ] [PMID: 12384382]
[37]
Sheng, C.; Zhang, W.; Ji, H.; Zhang, M.; Song, Y.; Xu, H.; Zhu, J.; Miao, Z.; Jiang, Q.; Yao, J.; Zhou, Y.; Zhu, J.; Lü, J. Structure-based optimization of azole antifungal agents by CoMFA, CoMSIA, and molecular docking. J. Med. Chem., 2006, 49(8), 2512-2525.
[http://dx.doi.org/10.1021/jm051211n ] [PMID: 16610794]
[38]
Park, J.S.; Yu, K.A.; Kang, T.H.; Kim, S.; Suh, Y.G. Discovery of novel indazole-linked triazoles as antifungal agents. Bioorg. Med. Chem. Lett., 2007, 17(12), 3486-3490.
[http://dx.doi.org/10.1016/j.bmcl.2007.03.074 ] [PMID: 17433670]
[39]
Liu, P.; Zhu, S.; Li, P.; Xie, W.; Jin, Y.; Sun, Q.; Wu, Q.; Sun, P.; Zhang, Y.; Yang, X.; Jiang, Y.; Zhang, D. Synthesis and SAR studies of biaryloxy-substituted triazoles as antifungal agents. Bioorg. Med. Chem. Lett., 2008, 18(11), 3261-3265.
[http://dx.doi.org/10.1016/j.bmcl.2008.04.056 ] [PMID: 18467095]
[40]
Pfaller, M.; Chaturvedi, V.; Espinel-Ingroff, A.; Ghannoum, M.; Gosey, L.L.; Odds, F.C. Reference method for broth dilution antifungal susceptibility testing of yeasts: approved standard second edition. CLSI document M27-A2 (ISBN 1-56238-469- 4).Clin Lab Stand Inst; , , 2008; 22, pp. 1-51.
[41]
Mellado, E.; Garcia-Effron, G.; Alcázar-Fuoli, L.; Melchers, W.J.; Verweij, P.E.; Cuenca-Estrella, M.; Rodríguez-Tudela, J.L. A new Aspergillus fumigatus resistance mechanism conferring in vitro cross-resistance to azole antifungals involves a combination of cyp51A alterations. Antimicrob. Agents Chemother., 2007, 51(6), 1897-1904.
[http://dx.doi.org/10.1128/AAC.01092-06 ] [PMID: 17371828]
[42]
Sadeghpour, H.; Khabnadideh, S.; Zomorodian, K.; Pakshir, K.; Hoseinpour, K.; Javid, N.; Faghih-Mirzaei, E.; Rezaei, Z. Design, synthesis, and biological activity of new triazole and nitro-triazole derivatives as antifungal agents. Molecules, 2017, 22(7), E1150.
[http://dx.doi.org/10.3390/molecules22071150 ] [PMID: 28698522]
[43]
Chai, X.; Zhang, J.; Yu, S.; Hu, H.; Zou, Y.; Zhao, Q.; Dan, Z.; Zhang, D.; Wu, Q. Design, synthesis, and biological evaluation of novel 1-(1H-1,2,4-triazole-1-yl)-2-(2,4-difluorophenyl)-3-substituted benzylamino-2-propanols. Bioorg. Med. Chem. Lett., 2009, 19(6), 1811-1814.
[http://dx.doi.org/10.1016/j.bmcl.2009.01.048 ] [PMID: 19231179]
[44]
Giraud, F.; Logé, C.; Pagniez, F.; Crepin, D.; Le Pape, P.; Le Borgne, M. Design, synthesis, and evaluation of 1-(N-benzylamino)-2-phenyl-3-(1H-1,2,4-triazol-1-yl)propan-2-ols as antifungal agents. Bioorg. Med. Chem. Lett., 2008, 18(6), 1820-1824.
[http://dx.doi.org/10.1016/j.bmcl.2008.02.027 ] [PMID: 18313295]
[45]
Giraud, F.; Guillon, R.; Logé, C.; Pagniez, F.; Picot, C.; Le Borgne, M.; Le Pape, P. Synthesis and structure-activity relationships of 2-phenyl-1-[(pyridinyl- and piperidinylmethyl)amino]-3-(1H-1,2,4-triazol-1-yl)propan-2-ols as antifungal agents. Bioorg. Med. Chem. Lett., 2009, 19(2), 301-304.
[http://dx.doi.org/10.1016/j.bmcl.2008.11.101 ] [PMID: 19091558]
[46]
Lebouvier, N.; Giraud, F.; Corbin, T.; Na, Y.M.; Le Baut, G.; Marchand, P.; Le Borgne, M. Efficient microwave-assisted synthesis of 1-(1H-indol-1-yl)-2-phenyl-3-(1H-1, 2, 4-triazol-1-yl) propan-2-ols as antifungal agents. Tetrahedron Lett., 2006, 47(36), 6479-6483.
[http://dx.doi.org/10.1016/j.tetlet.2006.03.199]
[47]
Chai, X.; Zhang, J.; Hu, H.; Yu, S.; Sun, Q.; Dan, Z.; Jiang, Y.; Wu, Q. Design, synthesis, and biological evaluation of novel triazole derivatives as inhibitors of cytochrome P450 14alpha-demethylase. Eur. J. Med. Chem., 2009, 44(5), 1913-1920.
[http://dx.doi.org/10.1016/j.ejmech.2008.11.007 ] [PMID: 19097674]
[48]
Aperis, G.; Mylonakis, E. Newer triazole antifungal agents: pharmacology, spectrum, clinical efficacy and limitations. Expert Opin. Investig. Drugs, 2006, 15(6), 579-602.
[http://dx.doi.org/10.1517/13543784.15.6.579 ] [PMID: 16732713]
[49]
Guan, Z.; Chai, X.; Yu, S.; Hu, H.; Jiang, Y.; Meng, Q.; Wu, Q. Synthesis, molecular docking, and biological evaluation of novel triazole derivatives as antifungal agents. Chem. Biol. Drug Des., 2010, 76(6), 496-504.
[http://dx.doi.org/10.1111/j.1747-0285.2010.01038.x ] [PMID: 20973917]
[50]
Guillon, R.; Giraud, F.; Logé, C.; Le Borgne, M.; Picot, C.; Pagniez, F.; Le Pape, P. Design of new antifungal agents: synthesis and evaluation of 1-[(1H-indol-5-ylmethyl)amino]-2-phenyl-3-(1H-1,2,4-triazol-1-yl)propan-2-ols. Bioorg. Med. Chem. Lett., 2009, 19(20), 5833-5836.
[http://dx.doi.org/10.1016/j.bmcl.2009.08.089 ] [PMID: 19762235]
[51]
Yu, S.; Chai, X.; Wang, Y.; Cao, Y.; Zhang, J.; Wu, Q.; Zhang, D.; Jiang, Y.; Yan, T.; Sun, Q. Triazole derivatives with improved in vitro antifungal activity over azole drugs. Drug Des. Devel. Ther., 2014, 8, 383-390.
[http://dx.doi.org/10.2147/DDDT.S58680 ] [PMID: 24748772]
[52]
Sheng, C.; Miao, Z.; Ji, H.; Yao, J.; Wang, W.; Che, X.; Dong, G.; Lü, J.; Guo, W.; Zhang, W. Three-dimensional model of lanosterol 14 alpha-demethylase from Cryptococcus neoformans: active-site characterization and insights into azole binding. Antimicrob. Agents Chemother., 2009, 53(8), 3487-3495.
[http://dx.doi.org/10.1128/AAC.01630-08 ] [PMID: 19470512]
[53]
Chen, S.H.; Sheng, C.Q.; Xu, X.H.; Jiang, Y.Y.; Zhang, W.N.; He, C. Identification of Y118 amino acid residue in Candida albicans sterol 14alpha-demethylase associated with the enzyme activity and selective antifungal activity of azole analogues. Biol. Pharm. Bull., 2007, 30(7), 1246-1253.
[http://dx.doi.org/10.1248/bpb.30.1246 ] [PMID: 17603162]
[54]
Ji, H.; Zhang, W.; Zhang, M.; Kudo, M.; Aoyama, Y.; Yoshida, Y.; Sheng, C.; Song, Y.; Yang, S.; Zhou, Y.; Lü, J.; Zhu, J. Structure-based de novo design, synthesis, and biological evaluation of non-azole inhibitors specific for lanosterol 14alpha-demethylase of fungi. J. Med. Chem., 2003, 46(4), 474-485.
[http://dx.doi.org/10.1021/jm020362c ] [PMID: 12570370]
[55]
Che, X.; Sheng, C.; Wang, W.; Cao, Y.; Xu, Y.; Ji, H.; Dong, G.; Miao, Z.; Yao, J.; Zhang, W. New azoles with potent antifungal activity: design, synthesis and molecular docking. Eur. J. Med. Chem., 2009, 44(10), 4218-4226.
[http://dx.doi.org/10.1016/j.ejmech.2009.05.018 ] [PMID: 19539408]
[56]
Jiang, Y.; Cao, Y.; Zhang, J.; Zou, Y.; Chai, X.; Hu, H.; Zhao, Q.; Wu, Q.; Zhang, D.; Jiang, Y.; Sun, Q. Design, synthesis and antifungal evaluation of 1-(2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)propyl)-1H-1,2,4-triazol-5(4H)-one. Eur. J. Med. Chem., 2011, 46(7), 3135-3141.
[http://dx.doi.org/10.1016/j.ejmech.2011.02.001 ] [PMID: 21354675]
[57]
Chai, X.; Zhang, J.; Cao, Y.; Zou, Y.; Wu, Q.; Zhang, D.; Jiang, Y.; Sun, Q. Design, synthesis and molecular docking studies of novel triazole as antifungal agent. Eur. J. Med. Chem., 2011, 46(7), 3167-3176.
[http://dx.doi.org/10.1016/j.ejmech.2011.04.022 ] [PMID: 21531485]
[58]
Chai, X.; Zhang, J.; Cao, Y.; Zou, Y.; Wu, Q.; Zhang, D.; Jiang, Y.; Sun, Q. New azoles with antifungal activity: Design, synthesis, and molecular docking. Bioorg. Med. Chem. Lett., 2011, 21(2), 686-689.
[http://dx.doi.org/10.1016/j.bmcl.2010.12.006 ] [PMID: 21190856]
[59]
Xu, J.; Cao, Y.; Zhang, J.; Yu, S.; Zou, Y.; Chai, X.; Wu, Q.; Zhang, D.; Jiang, Y.; Sun, Q. Design, synthesis and antifungal activities of novel 1,2,4-triazole derivatives. Eur. J. Med. Chem., 2011, 46(7), 3142-3148.
[http://dx.doi.org/10.1016/j.ejmech.2011.02.042 ] [PMID: 21420761]
[60]
Yu, S.; Wang, N.; Chai, X.; Wang, B.; Cui, H.; Zhao, Q.; Zou, Y.; Sun, Q.; Meng, Q.; Wu, Q. Synthesis and antifungal activity of the novel triazole derivatives containing 1,2,3-triazole fragment. Arch. Pharm. Res., 2013, 36(10), 1215-1222.
[http://dx.doi.org/10.1007/s12272-013-0063-0 ] [PMID: 23640383]
[61]
Xu, K.; Huang, L.; Xu, Z.; Wang, Y.; Bai, G.; Wu, Q.; Wang, X.; Yu, S.; Jiang, Y. Design, synthesis, and antifungal activities of novel triazole derivatives containing the benzyl group. Drug Des. Devel. Ther., 2015, 9, 1459-1467.
[PMID: 25792806]
[62]
Zou, Y.; Yu, S.; Li, R.; Zhao, Q.; Li, X.; Wu, M.; Huang, T.; Chai, X.; Hu, H.; Wu, Q. Synthesis, antifungal activities and molecular docking studies of novel 2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)propyl dithiocarbamates. Eur. J. Med. Chem., 2014, 74, 366-374.
[http://dx.doi.org/10.1016/j.ejmech.2014.01.009 ] [PMID: 24487187]
[63]
Yu, S.; Wang, L.; Wang, Y.; Song, Y.; Cao, Y.; Jiang, Y.; Sun, Q.; Wu, Q. Molecular docking, design, synthesis and antifungal activity study of novel triazole derivatives containing the 1,2,3-triazole group. RSC Advances, 2013, 3(32), 13486-13490.
[http://dx.doi.org/10.1039/c3ra41310a]
[64]
Yu, S.; Chai, X.; Wang, N.; Cui, H.; Zhao, Q.; Hu, H.; Zou, Y.; Sun, Q.; Wu, Q. Synthesis and antifungal activity of the novel triazole compounds. MedChemComm, 2013, 4(4), 704-708.
[http://dx.doi.org/10.1039/c3md20086h]
[65]
Wang, Y.; Xu, K.; Bai, G.; Huang, L.; Wu, Q.; Pan, W.; Yu, S. Synthesis and antifungal activity of novel triazole compounds containing piperazine moiety. Molecules, 2014, 19(8), 11333-11340.
[http://dx.doi.org/10.3390/molecules190811333 ] [PMID: 25090121]
[66]
Gatti, R.; Cavrini, V.; Roveri, P.; Luglio, G. Synthesis and antimycotic activity of some 3-(1-imidazolylmethyl)indoles. Arch. Pharm. (Weinheim), 1985, 318(2), 157-160.
[http://dx.doi.org/10.1002/ardp.19853180210 ] [PMID: 3994498]
[67]
Sugiyama, H.; Yokokawa, F.; Aoyama, T.; Shioiri, T. Synthetic studies of N-reverse prenylated indole. An efficient synthesis of antifungal indole alkaloids and N-reverse prenylated tryptophan. Tetrahedron Letters -. Tetrahedron Lett., 2001, 42, 7277-7280.
[http://dx.doi.org/10.1016/S0040-4039(01)01492-7]
[68]
Dandia, A.; Singh, R.; Khaturia, S.; Mérienne, C.; Morgant, G.; Loupy, A. Efficient microwave enhanced regioselective synthesis of a series of benzimidazolyl/triazolyl spiro [indole-thiazolidinones] as potent antifungal agents and crystal structure of spiro[3H-indole-3,2′-thiazolidine]-3‘(1,2,4-triazol-3-yl)-2,4’(1H)-dione. Bioorg. Med. Chem., 2006, 14(7), 2409-2417.
[http://dx.doi.org/10.1016/j.bmc.2005.11.025 ] [PMID: 16321543]
[69]
Tiwari, R.K.; Verma, A.K.; Chhillar, A.K.; Singh, D.; Singh, J.; Kasi Sankar, V.; Yadav, V.; Sharma, G.L.; Chandra, R. Synthesis and antifungal activity of substituted-10-methyl-1,2,3,4-tetrahydropyrazino[1,2-a]indoles. Bioorg. Med. Chem., 2006, 14(8), 2747-2752.
[http://dx.doi.org/10.1016/j.bmc.2005.11.054 ] [PMID: 16377197]
[70]
Lebouvier, N.; Pagniez, F.; Duflos, M.; Le Pape, P.; Na, Y.M.; Le Baut, G.; Le Borgne, M. Synthesis and antifungal activities of new fluconazole analogues with azaheterocycle moiety. Bioorg. Med. Chem. Lett., 2007, 17(13), 3686-3689.
[http://dx.doi.org/10.1016/j.bmcl.2007.04.038 ] [PMID: 17482460]
[71]
Pagniez, F.; Le Pape, P. New fluorometric screening test for possible antifungal drugs. J. Med. Mycol., 2001, 11, 73-78.
[72]
Pagniez, F.; Lebouvier, N.; Na, Y.M.; Ourliac-Garnier, I.; Picot, C.; Le Borgne, M.; Le Pape, P. Biological exploration of a novel 1,2,4-triazole-indole hybrid molecule as antifungal agent. J. Enzyme Inhib. Med. Chem., 2020, 35(1), 398-403.
[http://dx.doi.org/10.1080/14756366.2019.1705292 ] [PMID: 31899979]
[73]
Na, Y.M. Synthesis and activity of novel indole linked triazole derivatives as antifungal agents. Bull. Korean Chem. Soc., 2010, 31, 3467-3470.
[http://dx.doi.org/10.5012/bkcs.2010.31.11.3467]
[74]
Na, Y-M.; Le Borgne, M.; Pagniez, F.; Le Baut, G.; Le Pape, P. Synthesis and antifungal activity of new 1-halogenobenzyl-3-imidazolylmethylindole derivatives. Eur. J. Med. Chem., 2003, 38(1), 75-87.
[http://dx.doi.org/10.1016/S0223-5234(02)00005-3 ] [PMID: 12593918]
[75]
Na, Y-M. Synthesis and activity of novel 1-halogenobenzylindole linked triazole derivatives as antifungal agents. Bull. Korean Chem. Soc., 2011, 32(1), 307-310.
[http://dx.doi.org/10.5012/bkcs.2011.32.1.307]
[76]
Sorbera, L.; Bartroli, J.; Castañer, J. Albaconazole. Drugs of The Future - DRUG FUTURE, 2003, 28(6), 529-537.
[77]
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]
[78]
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]
[79]
Cao, X.; Sun, Z.; Cao, Y.; Wang, R.; Cai, T.; Chu, W.; Hu, W.; Yang, Y. Design, synthesis, and structure-activity relationship studies of novel fused heterocycles-linked triazoles with good activity and water solubility. J. Med. Chem., 2014, 57(9), 3687-3706.
[http://dx.doi.org/10.1021/jm4016284 ] [PMID: 24564525]
[80]
Xie, F.; Ni, T.; Zhao, J.; Pang, L.; Li, R.; Cai, Z.; Ding, Z.; Wang, T.; Yu, S.; Jin, Y.; Zhang, D.; Jiang, Y. Design, synthesis, and in vitro evaluation of novel antifungal triazoles. Bioorg. Med. Chem. Lett., 2017, 27(10), 2171-2173.
[http://dx.doi.org/10.1016/j.bmcl.2017.03.062 ] [PMID: 28372907]
[81]
Chai, X.; Yu, S.; Jiang, Y.; Zou, Y.; Wu, Q.; Zhang, D.; Jiang, Y.; Cao, Y.; Sun, Q. Design, synthesis, and biological evaluation of novel 1, 2, 4-triazole derivatives as antifungal agent. Arch. Pharm. Res., 2012, 35(11), 1895-1901.
[http://dx.doi.org/10.1007/s12272-012-1105-8 ] [PMID: 23212630]
[82]
Ding, Z.; Ni, T.; Xie, F.; Hao, Y.; Yu, S.; Chai, X.; Jin, Y.; Wang, T.; Jiang, Y.; Zhang, D. Design, synthesis, and structure-activity relationship studies of novel triazole agents with strong antifungal activity against Aspergillus fumigatus. Bioorg. Med. Chem. Lett., 2020, 30(4), 126951.
[http://dx.doi.org/10.1016/j.bmcl.2020.126951 ] [PMID: 31926784]
[83]
Thamban Chandrika, N.; Shrestha, S.K.; Ngo, H.X.; Tsodikov, O.V.; Howard, K.C.; Garneau-Tsodikova, S. Alkylated piperazines and piperazine-azole hybrids as antifungal agents. J. Med. Chem., 2018, 61(1), 158-173.
[http://dx.doi.org/10.1021/acs.jmedchem.7b01138 ] [PMID: 29256601]
[84]
Mahmoudi, Y.; Badali, H.; Hashemi, S.M.; Ansari, M.; Fakhim, H.; Fallah, M.; Shokrzadeh, M.; Emami, S. New potent antifungal triazole alcohols containing N-benzylpiperazine carbodithioate moiety: Synthesis, in vitro evaluation and in silico study. Bioorg. Chem., 2019, 90, 103060.
[http://dx.doi.org/10.1016/j.bioorg.2019.103060 ] [PMID: 31229796]
[85]
Ni, T.; Pang, L.; Cai, Z.; Xie, F.; Ding, Z.; Hao, Y.; Li, R.; Yu, S.; Chai, X.; Wang, T.; Jin, Y.; Zhang, D.; Jiang, Y. Design, synthesis, and in vitro antifungal evaluation of novel triazole derivatives bearing alkynyl side chains. J. Saudi Chem. Soc., 2019, 23(5), 576-585.
[http://dx.doi.org/10.1016/j.jscs.2018.10.003]
[86]
Rudramurthy, S.M.; Colley, T.; Abdolrasouli, A.; Ashman, J.; Dhaliwal, M.; Kaur, H.; Armstrong-James, D.; Strong, P.; Rapeport, G.; Schelenz, S.; Ito, K.; Chakrabarti, A. In vitro antifungal activity of a novel topical triazole PC945 against emerging yeast Candida auris. J. Antimicrob. Chemother., 2019, 74(10), 2943-2949.
[http://dx.doi.org/10.1093/jac/dkz280 ] [PMID: 31325309]
[87]
Colley, T.; Alanio, A.; Kelly, S.L.; Sehra, G.; Kizawa, Y.; Warrilow, A.G.S.; Parker, J.E.; Kelly, D.E.; Kimura, G.; Anderson-Dring, L.; Nakaoki, T.; Sunose, M.; Onions, S.; Crepin, D.; Lagasse, F.; Crittall, M.; Shannon, J.; Cooke, M.; Bretagne, S.; King-Underwood, J.; Murray, J.; Ito, K.; Strong, P.; Rapeport, G. In Vitro and In Vivo Antifungal Profile of a Novel and Long-Acting Inhaled Azole, PC945, on Aspergillus fumigatus Infection. Antimicrob. Agents Chemother., 2017, 61(5), 1-14.
[http://dx.doi.org/10.1128/AAC.02280-16 ] [PMID: 28223388]
[88]
Banfi, E.; Scialino, G.; Zampieri, D.; Mamolo, M.G.; Vio, L.; Ferrone, M.; Fermeglia, M.; Paneni, M.S.; Pricl, S. Antifungal and antimycobacterial activity of new imidazole and triazole derivatives. A combined experimental and computational approach. J. Antimicrob. Chemother., 2006, 58(1), 76-84.
[http://dx.doi.org/10.1093/jac/dkl182 ] [PMID: 16709593]
[89]
Rezaei, Z.; Khabnadideh, S.; Pakshir, K.; Hossaini, Z.; Amiri, F.; Assadpour, E. Design, synthesis, and antifungal activity of triazole and benzotriazole derivatives. Eur. J. Med. Chem., 2009, 44(7), 3064-3067.
[http://dx.doi.org/10.1016/j.ejmech.2008.07.012 ] [PMID: 18760508]
[90]
Liu, Y.; Ryan, M.E.; Lee, H-M.; Simon, S.; Tortora, G.; Lauzon, C.; Leung, M.K.; Golub, L.M. A chemically modified tetracycline (CMT-3) is a new antifungal agent. Antimicrob. Agents Chemother., 2002, 46(5), 1447-1454.
[http://dx.doi.org/10.1128/AAC.46.5.1447-1454.2002 ] [PMID: 11959581]
[91]
Kokil, G.R.; Rewatkar, P.V.; Gosain, S.; Aggarwal, S.; Verma, A.; Kalra, A.; Thareja, S. Synthesis and in vitro evaluation of novel 1, 2, 4-triazole derivatives as antifungal agents. Lett. Drug Des. Discov., 2010, 7(1), 46-49.
[http://dx.doi.org/10.2174/157018010789869415]
[92]
Hari Narayana Moorthy, N.S.; Vittal, U.B.; Karthikeyan, C.; Thangapandian, V.; Venkadachallam, A.P.; Trivedi, P. Synthesis, antifungal evaluation and in silico study of novel Schiff bases derived from 4-amino-5(3,5-dimethoxy-phenyl)-4H-1,2,4-triazol-3-thiol. Arab. J. Chem., 2017, 10, S3239-S3244.
[http://dx.doi.org/10.1016/j.arabjc.2013.12.021]
[93]
Mange, Y.J.; Isloor, A.M.; Malladi, S.; Isloor, S.; Fun, H-K. Synthesis and antimicrobial activities of some novel 1,2,4-triazole derivatives. Arab. J. Chem., 2013, 6(2), 177-181.
[http://dx.doi.org/10.1016/j.arabjc.2011.01.033]
[94]
Mackie, T.J.; McCartney, J.E.; Collee, J.G.; Mackie, T.J. Mackie & McCartney practical medical microbiology; Elsevier: Amsterdam, 1989.
[95]
Goyal, P.K.; Bhandari, A.; Rana, A.C.; Jain, C.B. Synthesis of some 3-substituted -4h-1, 2, 4-triazole derivatives with potent anti-inflammatory activity. Asian J. Pharma. Clin. Res., 2010, 3, 244-246.
[96]
Wu, W-N.; Jiang, Y-M.; Fei, Q.; Du, H-T. Synthesis and fungicidal activity of novel 1,2,4-triazole derivatives containing a pyrimidine moiety. Phosphorus Sulfur Silicon Relat. Elem., 2019, 194(12), 1171-1175.
[http://dx.doi.org/10.1080/10426507.2019.1633321]
[97]
Can, N.; Acar Çevik, U.; Sağlık, B.; Levent, S.; Korkut, B.; Özkay, Y.; Kaplancıklı, Z.; Koparal, A. Synthesis, molecular docking studies, and antifungal activity evaluation of new benzimidazole-triazoles as potential lanosterol 14 α -demethylase inhibitors. J. Chem., 2017, 2017, 1-15.
[http://dx.doi.org/10.1155/2017/9387102]
[98]
Ahirwar, D.L.S.; Jha, K. Synthesis and characterization of 1,2,4-triazole- pyridine hybrids as potential antimicrobial agents. Intl. J. Pharma. Clin. Res., 2017, 9(12), 702-709.
[99]
Ahirwar, J.; Ahirwar, D.; Lanjhiyana, S.; Jha, A.; Dewangan, D.; Badwaik, H. Synthesis, characterization, molecular modeling, and biological evaluation of 1,2,4-triazole-pyridine hybrids as potential antimicrobial agents. J. Heterocycl. Chem., 2018, 55(11), 2598-2606.
[http://dx.doi.org/10.1002/jhet.3319]
[100]
Wang, B-L.; Zhang, L-Y.; Zhan, Y-Z.; Zhang, Y.; Zhang, X.; Wang, L-Z.; Li, Z-M. Synthesis and biological activities of novel 1,2,4-triazole thiones and bis(1,2,4-triazole thiones) containing phenylpyrazole and piperazine moieties. J. Fluor. Chem., 2016, 184, 36-44.
[http://dx.doi.org/10.1016/j.jfluchem.2016.02.004]
[101]
Zhang, Y.; Zhan, Y-Z.; Ma, Y.; Hua, X-W.; Wei, W.; Zhang, X.; Song, H-B.; Li, Z-M.; Wang, B-L. Synthesis, crystal structure and 3D-QSAR studies of antifungal (bis-)1,2,4-triazole Mannich bases containing furyl and substituted piperazine moieties. Chin. Chem. Lett., 2018, 29(3), 441-446.
[http://dx.doi.org/10.1016/j.cclet.2017.08.035]
[102]
El Bialy, S.A.; Nagy, M.M.; Abdel-Rahman, H.M. Efficient regioselective three-component domino synthesis of 3-(1,2,4-Triazol-5-yl)-1,3-thiazolidin-4-ones as potent antifungal and antituberculosis agents. Arch. Pharm. (Weinheim), 2011, 344(12), 821-829.
[http://dx.doi.org/10.1002/ardp.201100001 ] [PMID: 21932255]
[103]
Ahmed, S.; Zayed, M.F.; El-Messery, S.M.; Al-Agamy, M.H.; Abdel-Rahman, H.M. Design, Synthesis, Antimicrobial Evaluation and Molecular Modeling Study of 1,2,4-Triazole-Based 4-Thiazolidinones. Molecules, 2016, 21(5), 568.
[http://dx.doi.org/10.3390/molecules21050568 ] [PMID: 27144547]
[104]
Yusuf, M.; Thakur, S. Synthesis, characterization & in vitro antimicrobial-antioxidant studies of novel N, 1-diphenyl-4,5-dihydro-1 H -1,2,4-triazol-3-amine derivatives. J. Heterocycl. Chem., 2019, 56(12), 3403-3413.
[http://dx.doi.org/10.1002/jhet.3714]
[105]
Ali, A.A.; Soliman, M.A.; Aouad, M.R.; Messali, M.; Rezki, N. Synthesis, characterization, and antimicrobial screening of novel 1,2,4-triazoles, 1,3,4-thiadiazoles, and 1,3,4-oxadiazoles bearing the indole moiety. Org. Prep. Proced. Int., 2019, 51(3), 270-286.
[http://dx.doi.org/10.1080/00304948.2019.1599791]
[106]
Frolova, Y. Design, synthesis, antimicrobial and antifungal activities of new 1,2,4-triazole derivatives containing 1h-tetrazole moiety. Ankara Universitesi Eczacilik Fakultesi Dergisi, 2020, 70-88.
[107]
Rao, D.V.; Prasad, A.; Spoorthy, Y.N.; Rao, D.; Ravindranath, L.K. Synthesis, characterization and antimicrobial evaluation of substituted 1,2,4-triazole thiones containing pyrazole moiety. J. Clin. Analyt. Med., 2015, 6, 590-595.
[http://dx.doi.org/10.4328/JCAM.2323]
[108]
Jóźwiak, M.; Stępień, K.; Wrzosek, M.; Olejarz, W.; Kubiak-Tomaszewska, G.; Filipowska, A.; Filipowski, W.; Struga, M. Synthesis, structural studies and biological evaluation of connections of thiosemicarbazide, 1,2,4-triazole and 1,3,4-thiadiazole with palmitic acid. Molecules, 2018, 23(4), 822.
[http://dx.doi.org/10.3390/molecules23040822 ] [PMID: 29614061]
[109]
Mohammad, H.; Elghazawy, N.H.; Eldesouky, H.E.; Hegazy, Y.A.; Younis, W.; Avrimova, L.; Hazbun, T.; Arafa, R.K.; Seleem, M.N. Discovery of a novel dibromoquinoline compound exhibiting potent antifungal and antivirulence activity that targets metal ion homeostasis. ACS Infect. Dis., 2018, 4(3), 403-414.
[http://dx.doi.org/10.1021/acsinfecdis.7b00215 ] [PMID: 29370698]
[110]
Aouad, M.R.; Mayaba, M.M.; Naqvi, A.; Bardaweel, S.K.; Al-Blewi, F.F.; Messali, M.; Rezki, N. Design, synthesis, in silico and in vitro antimicrobial screenings of novel 1,2,4-triazoles carrying 1,2,3-triazole scaffold with lipophilic side chain tether. Chem. Cent. J., 2017, 11(1), 117-117.
[http://dx.doi.org/10.1186/s13065-017-0347-4 ] [PMID: 29159721]
[111]
Gomha, S.; Edrees, M.; Muhammad, Z.; Kheder, N.; Melha, S.; Saad, A. Synthesis, characterization, and antimicrobial evaluation of some new 1,4-dihydropyridines-1,2,4-triazole hybrid compounds; Polycyc. Aromatic Compounds, 2020, pp. 1-13.
[112]
Behalo, M.; Aly, A.; Wasfy, A.; Mohamed, M. Synthesis of some novel 1,2,4-triazole derivatives as potential antimicrobial agents. Eur. J. Chem., 2013, 4, 92-97.
[http://dx.doi.org/10.5155/eurjchem.4.2.92-97.615]
[113]
Tratrat, C.; Haroun, M.; Paparisva, A.; Geronikaki, A.; Kamoutsis, C.; Ćirić, A.; Glamočlija, J.; Soković, M.; Fotakis, C.; Zoumpoulakis, P.; Bhunia, S.S.; Saxena, A.K. Design, synthesis and biological evaluation of new substituted 5-benzylideno-2-adamantylthiazol[3,2-b][1,2,4]triazol-6(5H)ones. Pharmacophore models for antifungal activity. Arab. J. Chem., 2018, 11(4), 573-590.
[http://dx.doi.org/10.1016/j.arabjc.2016.06.007]
[114]
Wang, T.; Yang, S.; Li, H.; Lu, A.; Wang, Z.; Yao, Y.; Wang, Q. Discovery, structural optimization, and mode of action of essramycin alkaloid and its derivatives as anti-tobacco mosaic virus and anti-phytopathogenic fungus agents. J. Agric. Food Chem., 2020, 68(2), 471-484.
[http://dx.doi.org/10.1021/acs.jafc.9b06006 ] [PMID: 31841334]
[115]
Fan, Z.; Shi, J.; Luo, N.; Ding, M.; Bao, X. Synthesis, crystal structure, and agricultural antimicrobial evaluation of novel quinazoline thioether derivatives incorporating the 1,2,4-triazolo[4,3-a]pyridine moiety. J. Agric. Food Chem., 2019, 67(42), 11598-11606.
[http://dx.doi.org/10.1021/acs.jafc.9b04733 ] [PMID: 31560195]
[116]
Fan, Z.; Yang, Z.; Zhang, H.; Mi, N.; Wang, H.; Cai, F.; Zuo, X.; Zheng, Q.; Song, H. Synthesis, crystal structure, and biological activity of 4-methyl-1,2,3-thiadiazole-containing 1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles. J. Agric. Food Chem., 2010, 58(5), 2630-2636.
[http://dx.doi.org/10.1021/jf9029628 ] [PMID: 20014761]
[117]
Zhao, B.; Fan, S.; Fan, Z.; Wang, H.; Zhang, N.; Guo, X.; Yang, D.; Wu, Q.; Yu, B.; Zhou, S. Discovery of Pyruvate Kinase as a Novel Target of New Fungicide Candidate 3-(4-Methyl-1,2,3-thiadiazolyl)-6-trichloromethyl-[1,2,4]-triazolo-[3,4- b][1,3,4]-thiadizole. J. Agric. Food Chem., 2018, 66(46), 12439-12452.
[http://dx.doi.org/10.1021/acs.jafc.8b03797 ] [PMID: 30350975]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 20
ISSUE: 24
Year: 2020
Page: [2235 - 2258]
Pages: 24
DOI: 10.2174/1568026620666200704140107
Price: $65

Article Metrics

PDF: 34
HTML: 2