{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T04:25:41Z","timestamp":1792211141987,"version":"4.4.0"},"reference-count":57,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2019,3,7]],"date-time":"2019-03-07T00:00:00Z","timestamp":1551916800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004586","name":"FAPERJ","doi-asserted-by":"publisher","award":["E -26\/2002.800\/2017"],"award-info":[{"award-number":["E -26\/2002.800\/2017"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"publisher","award":["303713\/2014-3"],"award-info":[{"award-number":["303713\/2014-3"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Capes","doi-asserted-by":"publisher","award":["scholarships"],"award-info":[{"award-number":["scholarships"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Sporotrichosis is a neglected fungal infection caused by Sporothrix spp., which have a worldwide distribution. The standard antifungal itraconazole has been recommended as a first-line therapy. However, failure cases in human and feline treatment have been reported in recent years. This study aimed to synthesize several \u03b1- and \u03b2-2,3-dihydrofuranaphthoquinones and evaluate them against Sporothrix schenckii and Sporothrix brasiliensis\u2014the main etiological agents of sporotrichosis in Brazil. The stability of these compounds was also investigated under different storage conditions for 3 months. The samples were removed at 0, 60, and 90 days and assessed by 1H-NMR, and their in vitro antifungal susceptibility was tested. Furthermore, we evaluated the superficial changes caused by the most effective and stable compounds using scanning electron microscopy and determined their effects when combined with itraconazole. Nine dihydrofuranaphthoquinones showed good antifungal activity and stability, with MIC values of 2\u201332 \u00b5M. Compounds 6 and 10 were the most active dihydrofuranaphthoquinones in vitro for both species; in fungi, these compounds induced yeast\u2013hyphae conversion and alteration in the hyphae and conidia structures. Compound 10 also exhibited a synergistic activity with itraconazole against S. schenckii, with a \u03a3FIC index value of 0.3. Our results indicate that Compounds 6 and 10 are potential candidates for the development of new antifungal agents for the treatment of sporotrichosis.<\/jats:p>","DOI":"10.3390\/molecules24050930","type":"journal-article","created":{"date-parts":[[2019,3,8]],"date-time":"2019-03-08T04:58:35Z","timestamp":1552021115000},"page":"930","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Synthesis, Stability Studies, and Antifungal Evaluation of Substituted \u03b1- and \u03b2-2,3-Dihydrofuranaphthoquinones against Sporothrix brasiliensis and Sporothrix schenckii"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0640-5079","authenticated-orcid":false,"given":"Patricia","family":"Garcia Ferreira","sequence":"first","affiliation":[{"name":"Departamento de Tecnologia Farmac\u00eautica, Faculdade de Farm\u00e1cia, Universidade Federal Fluminense, Niter\u00f3i-RJ 24241-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6576-6646","authenticated-orcid":false,"given":"Luana","family":"Pereira Borba-Santos","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Celular de Fungos, Instituto de Biof\u00edsica Carlos Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ-Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leticia Lorena","family":"Noronha","sequence":"additional","affiliation":[{"name":"Departamento de Tecnologia Farmac\u00eautica, Faculdade de Farm\u00e1cia, Universidade Federal Fluminense, Niter\u00f3i-RJ 24241-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Deckman Nicoletti","sequence":"additional","affiliation":[{"name":"Departamento de Tecnologia Farmac\u00eautica, Faculdade de Farm\u00e1cia, Universidade Federal Fluminense, Niter\u00f3i-RJ 24241-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcella","family":"de S\u00e1 Haddad Queiroz","sequence":"additional","affiliation":[{"name":"Departamento de Tecnologia Farmac\u00eautica, Faculdade de Farm\u00e1cia, Universidade Federal Fluminense, Niter\u00f3i-RJ 24241-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2042-3778","authenticated-orcid":false,"given":"Fernando","family":"de Carvalho da Silva","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e2nica, Instituto de Qu\u00edmica, Universidade Federal Fluminense, Niter\u00f3i-RJ 24210-141, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3659-5945","authenticated-orcid":false,"given":"S\u00f4nia","family":"Rozental","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Celular de Fungos, Instituto de Biof\u00edsica Carlos Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ-Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00e9bora","family":"Omena Futuro","sequence":"additional","affiliation":[{"name":"Departamento de Tecnologia Farmac\u00eautica, Faculdade de Farm\u00e1cia, Universidade Federal Fluminense, Niter\u00f3i-RJ 24241-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2166-766X","authenticated-orcid":false,"given":"Vitor","family":"Francisco Ferreira","sequence":"additional","affiliation":[{"name":"Departamento de Tecnologia Farmac\u00eautica, Faculdade de Farm\u00e1cia, Universidade Federal Fluminense, Niter\u00f3i-RJ 24241-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,3,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1017\/S0953756201004725","article-title":"The magnitude of fungal diversity: The 1.5 million species estimate revisited","volume":"105","author":"Hawksworth","year":"2001","journal-title":"Mycol. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1016\/S1473-3099(17)30319-5","article-title":"Recovery from serious fungal infections should be realisable for everyone","volume":"17","author":"Tudela","year":"2017","journal-title":"Lancet Infect. Dis."},{"key":"ref_3","unstructured":"(2018, November 19). Leading International Fungal Education. Available online: http:\/\/www.life-worldwide.org\/media-centre\/article\/the-burden-of-fungal-disease-new-evidence-to-show-the-scale-of-the-problem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1007\/s10096-017-2918-7","article-title":"Serious fungal infections in the Philippines","volume":"36","author":"Batac","year":"2017","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1590\/S1806-37132010000100019","article-title":"Fungal infections in immunocompromised patients","volume":"36","author":"Silva","year":"2010","journal-title":"J. Bras. Pneumol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1111\/j.1468-3083.2011.04389.x","article-title":"Report of 457 sporotrichosis cases from Jilin province, northeast China, a serious endemic region","volume":"27","author":"Song","year":"2013","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Ram\u00edrez Soto, M.C. (2015). Sporotrichosis: The Story of an Endemic Region in Peru over 28 Years (1985 to 2012). PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0127924"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1128\/CMR.00007-11","article-title":"Sporothrix schenckii and Sporotrichosis","volume":"24","author":"Barros","year":"2011","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1590\/abd1806-4841.2017279","article-title":"Sporotrichosis: An update on epidemiology, etiopathogenesis, laboratory and clinical therapeutics","volume":"92","author":"Macedo","year":"2017","journal-title":"An. Bras. Dermatol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Rodrigues, A.M., de Melo Teixeira, M., de Hoog, G.S., Schubach, T.M., Pereira, S.A., Fernandes, G.F., Bezerra, L.M., Felipe, M.S., and de Camardo, Z.P. (2013). Phylogenetic analysis reveals a high prevalence of Sporothrix brasiliensis in feline sporotrichosis outbreaks. PLoS Negl. Trop. Dis., 7.","DOI":"10.1371\/journal.pntd.0002281"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Montenegro, H., Rodrigues, A.M., Dias, M.A., da Silva, E.A., Bernardi, F., and de Camargo, Z.P. (2014). Feline sporotrichosis due to Sporothrix brasiliensis: An emerging animal infection in S\u00e3o Paulo, Brazil. BMC Vet. Res., 10.","DOI":"10.1186\/s12917-014-0269-5"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1093\/mmy\/myu062","article-title":"Global epidemiology of sporotrichosis","volume":"53","author":"Chakrabarti","year":"2015","journal-title":"Med. Mycol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"250","DOI":"10.11606\/S1413-95962011000300010","article-title":"Esporotricose","volume":"48","author":"Larsson","year":"2011","journal-title":"Braz. J. Vet. Res. Anim."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1590\/S0036-46652011000200006","article-title":"Cutaneous sporotrichosis treatment with potassium iodide. a 24 year experience in S\u00e3o Paulo State, Brazil","volume":"53","author":"Yamada","year":"2011","journal-title":"Rev. Inst. Med. Trop."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1093\/clinids\/22.1.46","article-title":"Treatment of lymphocutaneous and visceral sporotrichosis with fluconazole","volume":"22","author":"Kauffman","year":"1996","journal-title":"Clin. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.riam.2015.03.001","article-title":"Interference of melanin in the susceptibility profile of Sporothrix species to amphotericin B","volume":"33","author":"Mario","year":"2016","journal-title":"Rev. Iberoam. Micol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Almeida-Paes, R., Figueiredo-Carvalho, M.H., Brito-Santos, F., Almeida-Silva, F., Oliveira, M.M., and Zancop\u00e9-Oliveira, R.M. (2016). Melanins protect Sporothrix brasiliensis and Sporothrix schenckii from the antifungal effects of terbinafine. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0152796"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1590\/S0037-86822007000100012","article-title":"In vitro susceptibility of isolates of Sporothrix schenckii to terbinafine and itraconazole","volume":"40","author":"Meinerz","year":"2007","journal-title":"Rev. Soc. Bras. Med. Trop."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"272376","DOI":"10.1155\/2014\/272376","article-title":"Sporotrichosis: An Overview and Therapeutic Options","volume":"2014","author":"Mahajan","year":"2014","journal-title":"Dermatol. Res. Pract."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1093\/cid\/cir245","article-title":"Treatment of cutaneous sporotrichosis with itraconazole-study of 645 patients","volume":"52","author":"Barros","year":"2011","journal-title":"Clin. Infect. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4319","DOI":"10.1128\/JCM.42.9.4319-4320.2004","article-title":"In Vitro Susceptibilities of Isolates of Sporothrix schenckii to Itraconazole and Terbinafine","volume":"42","author":"Kohler","year":"2004","journal-title":"J. Clin. Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1093\/mmy\/myu085","article-title":"In vitro inhibitory activity of terpenic derivatives against clinical and environmental strains of the Sporothrix schenkii complex","volume":"53","author":"Brilhante","year":"2015","journal-title":"Med. Mycol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"164","DOI":"10.2174\/1568026618666180221115508","article-title":"Synthesis and Antifungal Activity of Coumarins Derivatives against Sporothrix spp.","volume":"18","author":"Forezi","year":"2018","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5324","DOI":"10.1016\/j.bmcl.2005.08.032","article-title":"Synthesis and biological evaluation of novel (L)-alpha-amino acid methyl ester, heteroalkyl, and aryl substituted 1,4-naphthoquinone derivatives as antifungal and antibacterial agents","volume":"15","author":"Tandon","year":"2005","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1099\/jmm.0.000517","article-title":"Chemical composition and cytotoxicity of extracts of marjoram and rosemary and their activity against Sporothrix brasiliensis","volume":"66","author":"Waller","year":"2017","journal-title":"J. Med. Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1111\/j.1439-0507.2008.01636.x","article-title":"Antifungal activities of compounds isolated from Kunth","volume":"52","author":"Johann","year":"2008","journal-title":"Mycoses"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/j.bjm.2016.07.017","article-title":"Cytotoxicity and anti-Sporothrix brasiliensis activity of the Origanum majorana Linn. oil","volume":"47","author":"Waller","year":"2016","journal-title":"Braz. J. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1590\/S0103-50532010000100024","article-title":"Novel 2-(R-phenyl)amino-3-(2-methylpropenyl)-[1,4]-naphthoquinones: Synthesis, characterization, electrochemical behavior and antitumor activity","volume":"21","author":"Francisco","year":"2010","journal-title":"J. Braz. Chem. Soc."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1002\/1099-1573(200102)15:1<44::AID-PTR685>3.0.CO;2-1","article-title":"In vitro and in vivo Leishmanicidal activity of 2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone (lapachol)","volume":"15","author":"Teixeira","year":"2001","journal-title":"Phytother. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.ejmech.2017.12.051","article-title":"Antimalarial naphthoquinones. Synthesis via click chemistry, in vitro activity, docking to PfDHODH and SAR of lapachol-based compounds","volume":"145","author":"Arantes","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5030","DOI":"10.1016\/j.bmc.2008.03.032","article-title":"Synthesis and anti-Trypanosoma cruzi activity of derivatives from nor-lapachones and lapachones","volume":"16","author":"Fernandes","year":"2008","journal-title":"Bioorg. Med. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1002\/ardp.200900162","article-title":"Synthesis of \u03b1- and \u03b2-Pyran Naphthoquinones as a New Class of Antitubercular Agents","volume":"343","author":"Ferreira","year":"2010","journal-title":"Arch. Pharm. Chem. Life Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1590\/0001-3765201820170815","article-title":"The Antifungal Activity of Naphthoquinones: An Integrative Review","volume":"90","author":"Futuro","year":"2018","journal-title":"An. Acad. Bras. Cienc."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.ejmech.2013.06.018","article-title":"Synthesis and antifungal activity of terpenyl-1,4-naphthoquinone and 1,4-anthracenedione derivatives","volume":"67","author":"Castro","year":"2013","journal-title":"Eur. J. Med. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1039\/c0md00074d","article-title":"Synthesis and biological evaluation of substituted \u03b1- and \u03b2-2,3-dihydrofuran naphthoquinones as potent anticandidal agents","volume":"1","author":"Freire","year":"2010","journal-title":"Med. Chem. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/1476-0711-13-26","article-title":"Antifungal activity of synthetic naphthoquinones against dermatophytes and opportunistic fungi: Preliminary mechanism-of-action tests","volume":"13","author":"Ferreira","year":"2014","journal-title":"Ann. Clin. Microbiol. Antimicrob."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1007\/s00044-016-1550-x","article-title":"Synthesis, antibacterial and antifungal activities of naphthoquinone derivatives: A structure-activity relationship study","volume":"25","author":"Barbero","year":"2016","journal-title":"Med. Chem. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"6398","DOI":"10.1016\/j.bmcl.2011.08.095","article-title":"Micelles catalyzed chemoselective synthesis \u2018in water\u2019 and biological evaluation of oxygen containing hetero-1,4-naphthoquinones as potential antifungal agents","volume":"21","author":"Tandon","year":"2011","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2016\/8135608","article-title":"Photostability and Photostabilization of Drugs and Drug Products","volume":"2016","author":"Ahmad","year":"2016","journal-title":"Int. J. Photoenergy"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2418","DOI":"10.1016\/j.ejmech.2010.02.023","article-title":"\u2018On water\u2019 assisted synthesis and biological evaluation of nitrogen and sulfur containing hetero-1,4-naphthoquinones as potent antifungal and antibacterial agents","volume":"45","author":"Tandon","year":"2010","journal-title":"Eur. J. Med. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3130","DOI":"10.1016\/j.ejmech.2009.03.006","article-title":"Design, synthesis and biological evaluation of novel nitrogen and sulfur containing hetero-1,4-naphthoquinones as potent antifungal and antibacterial agents","volume":"44","author":"Tandon","year":"2009","journal-title":"Eur. J. Med. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1016\/j.ejmech.2008.06.025","article-title":"2,3-Disubstituted-1,4-naphthoquinones, 12H-benzo[b]phenothiazine-6, 11-diones and related compounds: Synthesis and Biological evaluation as potential antiproliferative and antifungal agents","volume":"44","author":"Tandon","year":"2009","journal-title":"Eur. J. Med. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"6120","DOI":"10.1016\/j.bmc.2006.04.029","article-title":"Design, synthesis, and biological evaluation of 1,2,3-trisubstituted-1,4-dihydrobenzo[g]quinoxaline-5,10-diones and related compounds as antifungal and antibacterial agents","volume":"14","author":"Tandon","year":"2006","journal-title":"Bioorg. Med. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3288","DOI":"10.1016\/j.bmcl.2005.04.066","article-title":"Synthesis of (1,4)-naphthoquinono-[3,2-c]-1H-pyrazoles and their (1,4)-naphthohydroquinone derivatives as antifungal, antibacterial, and anticancer agents","volume":"15","author":"Tandon","year":"2005","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1016\/j.bmcl.2004.01.002","article-title":"Design, synthesis and evaluation of novel 1,4-naphthoquinone derivatives as antifungal and anticancer agents","volume":"14","author":"Tandon","year":"2004","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1007\/s00044-017-1789-x","article-title":"Exploring 1,2,3-triazole derivatives by using in vitro and in silico assays to target new antifungal agents and treat Candidiasis","volume":"26","author":"Santos","year":"2017","journal-title":"Med. Chem. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1590\/S0100-40422013000200023","article-title":"Guia para a Determina\u00e7\u00e3o da Estabilidade de Produtos Qu\u00edmicos","volume":"36","author":"Oriqui","year":"2013","journal-title":"Quim Nova"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"7705","DOI":"10.1016\/S0040-4020(01)00700-1","article-title":"CAN mediated oxidative addition of 2 hydroxinaphthoquinone to dienes: A facile synthesis of naphthofuranodiones","volume":"57","author":"Nair","year":"2001","journal-title":"Tetrahedron"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1007\/s11172-006-0480-z","article-title":"Chemistry of naphthazarin derivatives 13. Conformational analysis of 3-(alk-1-enyl)-2-hydroxy-1,4-naphthoquinones by quantum chemistry methods","volume":"55","author":"Glazunov","year":"2006","journal-title":"Russ. Chem. Bull."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4763","DOI":"10.1016\/j.bmc.2015.05.039","article-title":"Synthesis and anti-Trypanosoma cruzi activity of new 3-phenylthio-nor-b-lapachone derivatives","volume":"23","author":"Cardoso","year":"2015","journal-title":"Bioorg. Med. Chem."},{"key":"ref_51","unstructured":"Clinical and Laboratory Standards Institute (2008). Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts, Approved Standard, M27-A3, Clinical and Laboratory Standards Institute. [3rd ed.]."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/jac\/dkg301","article-title":"Synergy, antagonism, and what the chequerboard puts between them","volume":"52","author":"Odds","year":"2003","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_53","unstructured":"Lorian, V. (2005). Antimicrobial Combinations. Antibiotics in Laboratory Medicine, Lippincott Williams & Wilkins Co.. [5th ed.]."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2439","DOI":"10.3390\/molecules15042439","article-title":"Thermal Analysis Applied to Verapamil Hydrochloride Characterization in Pharmaceutical Formulations","volume":"15","author":"Yoshida","year":"2010","journal-title":"Molecules"},{"key":"ref_55","first-page":"1","article-title":"Thermal Analysis Methods in Pharmaceutical Quality Control","volume":"3","author":"Monajjemzadeh","year":"2015","journal-title":"J. Mol. Pharm. Org. Process. Res."},{"key":"ref_56","first-page":"29","article-title":"Thermal Analysis\u2014A Review of Techniques and Applications in the Pharmaceutical Sciences","volume":"13","author":"Stodghill","year":"2010","journal-title":"Am. Pharm. Rev."},{"key":"ref_57","first-page":"311","article-title":"Differential scanning calorimetry: Applications in drug development","volume":"2","author":"Clas","year":"1999","journal-title":"PSTT"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/5\/930\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:36:56Z","timestamp":1760186216000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/5\/930"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,7]]},"references-count":57,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2019,3]]}},"alternative-id":["molecules24050930"],"URL":"https:\/\/doi.org\/10.3390\/molecules24050930","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,7]]}}}