Two novel thiosemicarbazones and eight novel 2-{[1-(5-alkyl/arylalkylpyrazin-2-yl)ethylidene]hydrazono}-1,3-thiazolidin-4-ones were prepared and tested against a panel of eight fungal strains-Candida albicans ATCC 44859, Candida tropicalis 156, Candida krusei E 28, Candida glabrata 20/I, Trichosporon asahii 1188, Aspergillus fumigatus 231, Lichtheimia corymbifera 272, and Trichophyton interdigitale 445. 1,3-Thiazolidin-4-ones exhibited activity against all strains, the most potent derivative was 2-{[1-(5-butylpyrazin-2-yl)ethylidene]hydrazono}e-1,3-thiazolidin-4-one. Susceptibility of C. glabrata to the studied 1,3-thiazolidin-4-ones (minimum inhibitory concentrations (MICs) were in the range 0.57 to 2.78 mg/L) is of great interest as this opportunistic pathogen is poorly susceptible to azoles and becomes resistant to echinocandins. Antifungal potency of thiosemicarbazones was slightly lower than that of 1,3-thiazolidin-4-ones.

Department of Biological and Medical Sciences Faculty of Pharmacy in Hradec Kralove Charles University Heyrovskeho 1203 500 05 Hradec Kralove Czech Republic

Department of Clinical Microbiology University Hospital Hradec Kralove Sokolska 581 500 05 Hradec Kralove Czech Republic

Department of Inorganic and Organic Chemistry Faculty of Pharmacy in Hradec Kralove Charles University Heyrovskeho 1203 500 05 Hradec Kralove Czech Republic

Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Faculty of Pharmacy in Hradec Kralove Charles University Heyrovskeho 1203 500 05 Hradec Kralove Czech Republic

GlaxoSmithKline Hvezdova 1734 2c 140 00 Prague Czech Republic

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Casadevall A. The Emergence of Invasive Fungal Diseases among Humans. [(accessed on 28 September 2016)]. Available online: http://www.healio.com/infectious-disease/vaccine-preventable-diseases/news/print/infectious-disease-news/%7B2c458852-25bc-4818-a020-b3dfd61b9d06%7D/the-emergence-of-invasive-fungal-diseases-among-humans.

Kontoyiannis D. Emerging Resistance, Continuous Progress in Antifungal Drug Development. [(accessed on 28 September 2016)]. Available online: http://www.healio.com/infectious-disease/antimicrobials/news/print/infectious-disease-news/%7B2ba9bc1e-4639-41e4-81c7-07654f0eb25d%7D/emerging-resistance-continuous-progress-in-antifungal-drug-development.

Sundriyal S., Sharma R.K., Jain R. Current advances in antifungal targets and drug development. Curr. Med. Chem. 2006;13:1321–1335. doi: 10.2174/092986706776873023. PubMed DOI

Kollipara R., Peranteau A.J., Nawas Z.Y., Tong Y., Woc-Colburn L., Yan A.C., Lupi O., Tyring S.K. Emerging infectious diseases with cutaneous manifestations fungal, helminthic, protozoan and ectoparasitic infections. J. Am. Acad. Dermatol. 2016;75:19–30. doi: 10.1016/j.jaad.2016.04.032. PubMed DOI

Bojsen R., Regenberg B., Folkesson A. Persistence and drug tolerance in pathogenic yeast. Curr. Genet. 2016 doi: 10.1007/s00294-016-0613-3. PubMed DOI

Sanglard D. Emerging threats in antifungal-resistant fungal pathogens. Front. Med. 2016;3:11. doi: 10.3389/fmed.2016.00011. PubMed DOI PMC

Kolaczkowska A., Kolaczkowski M. Drug resistance mechanisms and their regulation in non-albicans Candida species. J. Antimicrob. Chemother. 2016;71:1438–1450. doi: 10.1093/jac/dkv445. PubMed DOI

Gupta A.K., Daigle D., Carviel J.L. The role of biofilms in onychomycosis. J. Am. Acad. Dermatol. 2016;74:1241–1246. doi: 10.1016/j.jaad.2016.01.008. PubMed DOI

Wiederhold N.P., Patterson T.F. What's new in antifungals: An update on the in vitro activity and in vivo efficacy of new and investigational antifungal agents. Curr. Opin. Infect. Dis. 2015;28:539–546. doi: 10.1097/QCO.0000000000000203. PubMed DOI

Seneviratne C.J., Rosa E.A. Editorial: Antifungal drug discovery: New theories and new therapies. Front. Microbiol. 2016;7:728. doi: 10.3389/fmicb.2016.00728. PubMed DOI PMC

Gupta A.K., Studholme C. Novel investigational therapies for onychomycosis: An update. Expert Opin. Investig. Drugs. 2016;25:297–305. doi: 10.1517/13543784.2016.1142529. PubMed DOI

Brown F.C. 4-Thiazolidinones. Chem. Rev. 1961;61:463–521. doi: 10.1021/cr60213a002. DOI

Singh S.P., Parmar S.S., Raman K., Stenberg V.I. Chemistry and biological activity of thiazolidinones. Chem. Rev. 1981;81:175–203. doi: 10.1021/cr00042a003. DOI

Lesyk R.B., Zimenkovsky B.S. 4-Thiazolidones: Centenarian history, current status and perspectives for modern organic and medicinal chemistry. Curr. Org. Chem. 2004;8:1547–1577. doi: 10.2174/1385272043369773. DOI

Hamama W.S., Ismail M.A., Shaaban S., Zoorob H.H. Progress in the chemistry of 4-thiazolidinones. J. Heterocycl. Chem. 2008;45:939–956. doi: 10.1002/jhet.5570450401. DOI

Verma A., Saraf S.K. 4-Thiazolidinone: A biologically active scaffold. Eur. J. Med. Chem. 2008;43:897–905. doi: 10.1016/j.ejmech.2007.07.017. PubMed DOI

Jain A.K., Vaidya A., Ravichandran V., Kashaw S.K., Agrawal R.K. Recent developments and biological activities of thiazolidinone derivatives: A review. Bioorg. Med. Chem. 2012;20:3378–3395. doi: 10.1016/j.bmc.2012.03.069. PubMed DOI

Tripathi A.C., Gupta S.J., Fatima G.N., Sonar P.K., Verma A., Saraf S.K. 4-Thiazolidinones: The advances continue. Eur. J. Med. Chem. 2014;72:52–77. doi: 10.1016/j.ejmech.2013.11.017. PubMed DOI

Mashrai A., Dar A.M., Mir S., Shamsuzzaman Strategies for the synthesis of thiazolidinone heterocycles. Med. Chem. (Los Angeles) 2016;6:280–291. doi: 10.4172/2161-0444.1000358. DOI

Opletalova V., Kalinowski D.S., Vejsova M., Kunes J., Pour M., Jampilek J., Buchta V., Richardson D.R. Identification and characterization of thiosemicarbazones with antifungal and antitumor effects: Cellular iron chelation mediating cytotoxic activity. Chem. Res. Toxicol. 2008;21:1878–1889. doi: 10.1021/tx800182k. PubMed DOI

Opletalova V., Dolezel J. Thiosemicarbazones and their antimycobacterial effects. Ceska Slov. Farm. 2013;62:78–83. PubMed

Vontor T., Palat K., Oswald J., Odlerova Z. Antituberculotics. XXXII. Functional derivatives of 5-methyl-2-pyrazinecarboxylic acid. Cesk. Farm. 1985;34:74–78.

Vontor T., Palat K., Odlerova Z. Antituberculotics XLI. Functional derivatives of 5-alkyl-2-pyrazinecarboxylic acid. Cesk. Farm. 1987;36:277–280.

Dlabal K., Palat K., Lycka A., Odlerova Z. Synthesis and 1H and 13C NMR spectra of sulfur derivatives of pyrazine derived from amidation product of 2-chloropyrazine and 6-chloro-2-pyrazinecarbonitrile. Tuberculostatic activity. Collect. Czech. Chem. Commun. 1990;55:2493–2501. doi: 10.1135/cccc19902493. DOI

Krinkova J., Dolezal M., Hartl J., Buchta V., Pour M. Synthesis and biological activity of 5-alkyl-6-(alkylsulfanyl)- or 5-alkyl-6-(arylsulfanyl)pyrazine-2-carboxamides and corresponding thioamides. Farmaco. 2002;57:71–78. doi: 10.1016/S0014-827X(01)01156-9. PubMed DOI

Dolezal M., Zitko J., Osicka Z., Kunes J., Vejsova M., Buchta V., Dohnal J., Jampilek J., Kralova K. Synthesis, antimycobacterial, antifungal and photosynthesis-inhibiting activity of chlorinated N-phenylpyrazine-2-carboxamides. Molecules. 2010;15:8567–8581. doi: 10.3390/molecules15128567. PubMed DOI PMC

Servusova B., Eibinova D., Dolezal M., Kubicek V., Paterova P., Pesko M., Kralova K. Substituted N-benzylpyrazine-2-carboxamides: Synthesis and biological evaluation. Molecules. 2012;17:13183–13198. doi: 10.3390/molecules171113183. PubMed DOI PMC

Zitko J., Servusova B., Paterova P., Mandikova J., Kubicek V., Kucera R., Hrabcova V., Kunes J., Soukup O., Dolezal M. Synthesis, Antimycobacterial Activity and In Vitro Cytotoxicity of 5-Chloro-N-phenylpyrazine-2-carboxamides. Molecules. 2013;18:14807–14825. doi: 10.3390/molecules181214807. PubMed DOI PMC

Jandourek O., Dolezal M., Kunes J., Kubicek V., Paterova P., Pesko M., Buchta V., Kralova K., Zitko J. New potentially active pyrazinamide derivatives synthesized under microwave conditions. Molecules. 2014;19:9318–9338. doi: 10.3390/molecules19079318. PubMed DOI PMC

Semelkova L., Konecna K., Paterova P., Kubicek V., Kunes J., Novakova L., Marek J., Naesens L., Pesko M., Kralova K., et al. Synthesis and Biological Evaluation of N-Alkyl-3-(alkylamino)-pyrazine-2-carboxamides. Molecules. 2015;20:8687–8711. doi: 10.3390/molecules20058687. PubMed DOI PMC

Opletalova V., Domonhedo C. Methods for preparation of acetylpyrazines. Chem. Listy. 1999;93:15–18.

Ried W., Russ T. Homolytic acylation of methyl 3-amino-2-pyrazinecarboxylates. Synthesis. 1991:581–582. doi: 10.1055/s-1991-26521. DOI

Opletalova V., Hartl J., Patel A., Boulton M. Homolytic acetylation of 2,5-dimethylpyrazine. Collect. Czech. Chem. Commun. 1995;60:1551–1554. doi: 10.1135/cccc19951551. DOI

Fontana F., Minisci F., Nogueira Barbosa M.C., Vismara E. Homolytic acylation of protonated pyridines and pyrazines with α-keto acids: The problem of monoacylation. J. Org. Chem. 1991;56:2866–2869. doi: 10.1021/jo00008a050. DOI

Sato N., Kadota H. Studies on pyrazine. 23. Homolytic acylation of 2-amino-3-cyanopyrazine and related compounds with α-keto acids: A synthesis of 5-acyl-3-aminopyrazinecarboxylic acid derivatives. J. Heterocycl. Chem. 1992;29:1685–1688. doi: 10.1002/jhet.5570290702. DOI

Punta C., Minisci F. Minisci reaction: A friedel-crafts type process with opposite reactivity and selectivity. Selective homolytic alkylation, acylation, carboxylation and carbamoylation of heterocyclic aromatic bases. Trends Heterocycl. Chem. 2008;13:1–68. doi: 10.1002/chin.201046230. DOI

Opletalova V., Hartl J., Domonhedo C., Patel A. Homolytic acetylation of 2-pyrazinecarbonitrile. Folia Pharm. Univ. Carol. 1999;24:29–32.

Kucerova-Chlupacova M., Kunes J., Buchta V., Vejsova M., Opletalova V. Novel pyrazine analogs of chalcones: Synthesis and evaluation of their antifungal and antimycobacterial activity. Molecules. 2015;20:1104–1117. doi: 10.3390/molecules20011104. PubMed DOI PMC

Kucerova-Chlupacova M., Vyskovska-Tyllova V., Richterova-Finkova L., Kunes J., Buchta V., Vejsova M., Paterova P., Semelkova L., Jandourek O., Opletalova V. Novel halogenated pyrazine-based chalcones as potential antimicrobial drugs. Molecules. 2016;21:1421. doi: 10.3390/molecules21111421. PubMed DOI PMC

Brown F.C., Bradsher C.K., Bond S.M. Mildew-preventing activity of rhodanine derivatives. Some 5-arylidene derivatives. Ind. Eng. Chem. 1953;45:1030–1033. doi: 10.1021/ie50521a047. DOI

Bluestone H. The Use of Cyclic, Nitrogen- and Sulfur-Containing Compounds as Fungicides. DE1019122B. German Patent. 1957 Nov 7;

Junghaehnel R., Renckhoff G., Thewalt K. Bacteriostat and Fungistat Compositions Containing N,S-Heterocyclic Compounds. US3681496A. U.S. Patent. 1972 Aug 1;

Legocki J., Matysiak J., Niewiadomy A., Kostecka M. Synthesis and fungistatic activity of new groups of 2,4-dihydroxythiobenzoyl derivatives against phytopathogenic fungi. J. Agric. Food Chem. 2003;51:362–368. doi: 10.1021/jf0206769. PubMed DOI

Kostecka M. Synthesis of a new group of aliphatic hydrazide derivatives and the correlations between their molecular structure and biological activity. Molecules. 2012;17:3560–3573. doi: 10.3390/molecules17033560. PubMed DOI PMC

Chauhan K., Sharma M., Singh P., Kumar V., Shukla P.K., Siddiqi M.I., Chauhan P.M.S. Discovery of a new class of dithiocarbamates and rhodanine scaffolds as potent antifungal agents: Synthesis, biology and molecular docking. Med. Chem. Commun. 2012;3:1104–1110. doi: 10.1039/c2md20109g. DOI

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. doi: 10.1016/j.ejmech.2014.01.009. PubMed DOI

Wiles D.M., Suprunchuk T. Antifungal activity of the thiosemicarbazones of some heterocyclic aldehydes. J. Med. Chem. 1971;14:252–254. doi: 10.1021/jm00285a023. PubMed DOI

Addor R.W., Lamb G. Thiosemicarbazone Fungicides. US3824317A. U.S. Patent. 1974 Jul 16;

Liberta A.E., West D.X. Antifungal and antitumor activity of heterocyclic thiosemicarbazones and their metal complexes: Current status. Biometals. 1992;5:121–126. doi: 10.1007/BF01062223. PubMed DOI

Reis D.C., Despaigne A.A.R., Da Silva J.G., Silva N.F., Vilela C.F., Mendes I.C., Takahashi J.A., Beraldo H. Structural studies and investigation on the activity of imidazole-derived thiosemicarbazones and hydrazones against crop-related fungi. Molecules. 2013;18:12645–12662. doi: 10.3390/molecules181012645. PubMed DOI PMC

Degola F., Morcia C., Bisceglie F., Mussi F., Tumino G., Ghizzoni R., Pelosi G., Terzi V., Buschini A., Restivo F.M., et al. In vitro evaluation of the activity of thiosemicarbazone derivatives against mycotoxigenic fungi affecting cereals. Int. J. Food Microbiol. 2015;200:104–111. doi: 10.1016/j.ijfoodmicro.2015.02.009. PubMed DOI

Altintop M.D., Atli O., Ilgin S., Demirel R., Ozdemir A., Kaplancikli Z.A. Synthesis and biological evaluation of new naphthalene substituted thiosemicarbazone derivatives as potent antifungal and anticancer agents. Eur. J. Med. Chem. 2016;108:406–414. doi: 10.1016/j.ejmech.2015.11.041. PubMed DOI

Meher S.S., Naik S., Behera R.K., Nayak A. Studies on thiazolidinones. Part XI: Synthesis and fungitoxicities of thiazolidinones, thiohydantoins and their derivatives derived from thiosemicarbazones. J. Indian Chem. Soc. 1981;58:274–276. doi: 10.1002/chin.198134221. DOI

Naik H., Naik S.K., Meher S.S., Nayak A. Studies on thiazolidinones. Part XIII: Synthesis and antimicrobial activities of thiazolidinones and their derivatives possessing, oxadiazole and isothiazole moieties. J. Indian Chem. Soc. 1983;60:674–678.

Mohan J., Chadha V.K., Chaudhary H.S., Sharma B.D., Pujari H.K., Mohapatra L.N. Heterocyclic systems containing bridgehead nitrogen atom. XIII. Antifungal and antibacterial activities of thiazole and thiazolidinone derivatives. Indian J. Exp. Biol. 1972;10:37–40. PubMed

Kumar D., Sharma R.C. Synthesis and Antimicrobial Activity of Some New 4-Thiazolidinones Derived from Heterocyclic Schiff Bases. J. Indian Chem. Soc. 2002;79:284–285. doi: 10.1002/chin.200305140. DOI

Nizami S.A., Gurumurthy M., Chattarjee S.J., Panda D. Evaluation of antimicrobial potency of some synthesized thiazolidin-4-one substituted 1,2,4-triazoles. J. Adv. Pharm. Res. 2010;1:26–35.

Pan B., Huang R.-Z., Han S.-Q., Qu D., Zhu M.-L., Wei P., Ying H.-J. Design, synthesis, and antibiofilm activity of 2-arylimino-3-aryl-thiazolidine-4-ones. Bioorg. Med. Chem. Lett. 2010;20:2461–2464. doi: 10.1016/j.bmcl.2010.03.013. PubMed DOI

Pan B., Huang R., Zheng L., Chen C., Han S., Qu D., Zhu M., Wei P. Thiazolidione derivatives as novel antibiofilm agents: Design, synthesis, biological evaluation, and structure-activity relationships. Eur. J. Med. Chem. 2011;46:819–824. doi: 10.1016/j.ejmech.2010.12.014. PubMed DOI

Panzariu A.-T., Apotrosoaei M., Vasincu I.M., Dragan M., Constantin S., Buron F., Routier S., Profire L., Tuchilus C. Synthesis and biological evaluation of new 1,3-thiazolidine-4-one derivatives of nitro-l-arginine methyl ester. Chem. Cent. J. 2016;10:6. doi: 10.1186/s13065-016-0151-6. PubMed DOI PMC

De Monte C., Carradori S., Bizzarri B., Bolasco A., Caprara F., Mollica A., Rivanera D., Mari E., Zicari A., Akdemir A., et al. Anti-candida activity and cytotoxicity of a large library of new N-substituted-1,3-thiazolidin-4-one derivatives. Eur. J. Med. Chem. 2016;107:82–96. doi: 10.1016/j.ejmech.2015.10.048. PubMed DOI

Secci D., Carradori S., Bizzarri B., Chimenti P., De Monte C., Mollica A., Rivanera D., Zicari A., Mari E., Zengin G., et al. Novel 1,3-thiazolidin-4-one derivatives as promising anti-Candida agents endowed with anti-oxidant and chelating properties. Eur. J. Med. Chem. 2016;117:144–156. doi: 10.1016/j.ejmech.2016.04.012. PubMed DOI

Shih M.H., Xu Y.Y., Yang Y.S., Lin G.L. A facile synthesis and antimicrobial activity evaluation of sydnonyl-substituted thiazolidine derivatives. Molecules. 2015;20:6520–6532. doi: 10.3390/molecules20046520. PubMed DOI PMC

Hozien Z.A. Synthesis of some new heterocyclic systems derived from 2-acetylbenzimidazole. J. Chem. Technol. Biotechnol. 1993;57:335–341. doi: 10.1002/jctb.280570407. PubMed DOI

Clinical and Laboratory Standards Institute (CLSI) Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts; Approved Standard. 3rd ed. Clinical and Laboratory Standards Institute; Wayne, PA, USA: 2008.

Clinical and Laboratory Standards Institute (CLSI) Reference Method for Broth Dilution Antifungal Susceptibility Testing of Filamentous Fungi; Approved Standard. 2nd ed. Clinical and Laboratory Standards Institute; Wayne, PA, USA: 2008.

Opletalova V., Hartl J., Patel A., Palat K., Jr., Buchta V. Ring substituted 3-phenyl-1-(2-pyrazinyl)-2-propen-1-ones as potential photosynthesis-inhibiting, antifungal and antimycobacterial agents. Farmaco. 2002;57:135–144. doi: 10.1016/S0014-827X(01)01187-9. PubMed DOI

Opletalova V., Pour M., Kunes J., Buchta V., Silva L., Kralova K., Chlupacova M., Meltrova D., Peterka M., Poslednikova M. Synthesis and biological evaluation of (E)-3-(Nitrophenyl)-1-(pyrazin-2-yl)prop-2-en-1-ones. Collect. Czech. Chem. Commun. 2006;71:44–58. doi: 10.1135/cccc20060044. DOI

Paramythiotou E., Frantzeskaki F., Flevari A., Armaganidis A., Dimopoulos G. Invasive fungal infections in the ICU: How to approach, how to treat. Molecules. 2014;19:1085–1119. doi: 10.3390/molecules19011085. PubMed DOI PMC

Verweij P.E., Ananda-Rajah M., Andes D., Arendrup M.C., Bruggemann R.J., Chowdhary A., Cornely O.A., Denning D.W., Groll A.H., Izumikawa K., et al. International expert opinion on the management of infection caused by azole-resistant Aspergillus fumigatus. Drug Resist. Updat. 2015;21–22:30–40. doi: 10.1016/j.drup.2015.08.001. PubMed DOI

Coelho C., Casadevall A. Cryptococcal therapies and drug targets: The old, the new and the promising. Cell Microbiol. 2016;18:792–799. doi: 10.1111/cmi.12590. PubMed DOI PMC

Liu N., Wang C., Su H., Zhang W., Sheng C. Strategies in the discovery of novel antifungal scaffolds. Future Med. Chem. 2016;8:1435–1454. doi: 10.4155/fmc-2016-0020. PubMed DOI

Miceli M.H., Diaz J.A., Lee S.A. Emerging opportunistic yeast infections. Lancet Infect. Dis. 2011;11:142–151. doi: 10.1016/S1473-3099(10)70218-8. PubMed DOI

Rodriguez-Gutierrez G., Carrillo-Casas E.M., Arenas R., Garcia-Mendez J.O., Toussaint S., Moreno-Morales M.E., Schcolnik-Cabrera A.A., Xicohtencatl-Cortes J., Hernandez-Castro R. Mucormycosis in a non-Hodgkin lymphoma patient caused by Syncephalastrum racemosum: Case report and review of literature. Mycopathologia. 2015;180:89–93. doi: 10.1007/s11046-015-9878-1. PubMed DOI

Perez-Torrado R., Querol A. Opportunistic strains of Saccharomyces cerevisiae: A potential risk sold in food products. Front. Microbiol. 2016;6:1522. doi: 10.3389/fmicb.2015.01522. PubMed DOI PMC

Dioverti M.V., Cawcutt K.A., Abidi M., Sohail M.R., Walker R.C., Osmon D.R. Gastrointestinal mucormycosis in immunocompromised hosts. Mycoses. 2015;58:714–718. doi: 10.1111/myc.12419. PubMed DOI

Svobodova L., Bednarova D., Ruzicka F., Chrenkova V., Dobias R., Mallatova N., Buchta V., Kocmanova I., Olisarova P., Stromerova N., et al. High frequency of Candida fabianii among clinical isolates biochemically identified as Candida pelliculosa and Candida utilis. Mycoses. 2016;59:241–246. doi: 10.1111/myc.12454. PubMed DOI

Glockner A., Cornely O.A. Candida glabrata: Unique features and challenges in the clinical management of invasive infections. Mycoses. 2015;58:445–450. doi: 10.1111/myc.12348. PubMed DOI

Bolotin-Fukuhara M., Fairhead C. Candida glabrata: A deadly companion? Yeast. 2014;31:279–288. doi: 10.1002/yea.3019. PubMed DOI

Arendrup M.C., Perlin D.S. Echinocandin resistance: An emerging clinical problem? Curr. Opin. Infect. Dis. 2014;27:484–492. doi: 10.1097/QCO.0000000000000111. PubMed DOI PMC

Shields R.K., Nguyen M.H., Clancy C.J. Clinical perspectives on echinocandin resistance among Candida species. Curr. Opin. Infect. Dis. 2015;28:514–522. doi: 10.1097/QCO.0000000000000215. PubMed DOI PMC

Krogh-Madsen M., Arendrup M.C., Heslet L., Knudsen J.D. Amphotericin B and caspofungin resistance in Candida glabrata isolates recovered from a critically ill patient. Clin. Infect. Dis. 2006;42:938–944. doi: 10.1086/500939. PubMed DOI

Opletalova V., Patel A., Boulton M., Dundrova A., Lacinova E., Prevorova M., Appeltauerova M., Coufalova M. 5-alkyl-2-pyrazinecarboxamides, 5-alkyl-2-pyrazinecarbonitriles and 5-alkyl-2-acetylpyrazines as synthetic intermediates for antiinflammatory agents. Collect. Czech. Chem. Commun. 1996;61:1093–1101. doi: 10.1135/cccc19961093. DOI

Kucerova-Chlupacova M., Opletalova V., Jampilek J., Dolezel J., Dohnal J., Pour M., Kunes J., Vorisek V. New hydrophobicity constants of substituents in pyrazine rings derived from RP-HPLC study. Collect. Czech. Chem. Commun. 2008;73:1–18. doi: 10.1135/cccc20080001. DOI