{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T05:58:10Z","timestamp":1788328690500,"version":"build-2803163510"},"reference-count":73,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,3,7]],"date-time":"2021-03-07T00:00:00Z","timestamp":1615075200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["552276\/2011-1"],"award-info":[{"award-number":["552276\/2011-1"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["88882.449039\/2019-01"],"award-info":[{"award-number":["88882.449039\/2019-01"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Candida albicans is the most common species isolated from nosocomial bloodstream infections. Due to limited therapeutic arsenal and increase of drug resistance, there is an urgent need for new antifungals. Therefore, the antifungal activity against C. albicans and in vivo toxicity of a 1,3,4-oxadiazole compound (LMM6) was evaluated. This compound was selected by in silico approach based on chemical similarity. LMM6 was highly effective against several clinical C. albicans isolates, with minimum inhibitory concentration values ranging from 8 to 32 \u00b5g\/mL. This compound also showed synergic effect with amphotericin B and caspofungin. In addition, quantitative assay showed that LMM6 exhibited a fungicidal profile and a promising anti-biofilm activity, pointing to its therapeutic potential. The evaluation of acute toxicity indicated that LMM6 is safe for preclinical trials. No mortality and no alterations in the investigated parameters were observed. In addition, no substantial alteration was found in Hippocratic screening, biochemical or hematological analyzes. LMM6 (5 mg\/kg twice a day) was able to reduce both spleen and kidneys fungal burden and further, promoted the suppresses of inflammatory cytokines, resulting in infection control. These preclinical findings support future application of LMM6 as potential antifungal in the treatment of invasive candidiasis.<\/jats:p>","DOI":"10.3390\/pathogens10030314","type":"journal-article","created":{"date-parts":[[2021,3,7]],"date-time":"2021-03-07T21:52:15Z","timestamp":1615153935000},"page":"314","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Fungicidal Activity of a Safe 1,3,4-Oxadiazole Derivative Against Candida albicans"],"prefix":"10.3390","volume":"10","author":[{"given":"Daniella Renata","family":"Faria","sequence":"first","affiliation":[{"name":"Laboratory of Medical Mycology, Department of Clinical Analysis and Biomedicine, State University of Maring\u00e1 (UEM), Maring\u00e1, Paran\u00e1 87020-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel Cabral","family":"Melo","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Mycology, Department of Clinical Analysis and Biomedicine, State University of Maring\u00e1 (UEM), Maring\u00e1, Paran\u00e1 87020-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glaucia Sayuri","family":"Arita","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Mycology, Department of Clinical Analysis and Biomedicine, State University of Maring\u00e1 (UEM), Maring\u00e1, Paran\u00e1 87020-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2899-2657","authenticated-orcid":false,"given":"Karina Mayumi","family":"Sakita","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Mycology, Department of Clinical Analysis and Biomedicine, State University of Maring\u00e1 (UEM), Maring\u00e1, Paran\u00e1 87020-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franciele Abigail Vilugron","family":"Rodrigues-Vendramini","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Mycology, Department of Clinical Analysis and Biomedicine, State University of Maring\u00e1 (UEM), Maring\u00e1, Paran\u00e1 87020-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isis Regina Grenier","family":"Capoci","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Mycology, Department of Clinical Analysis and Biomedicine, State University of Maring\u00e1 (UEM), Maring\u00e1, Paran\u00e1 87020-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5952-6945","authenticated-orcid":false,"given":"Tania Cristina Alexandrino","family":"Becker","sequence":"additional","affiliation":[{"name":"Laboratory of General Pathology, Department of Basic Health Sciences, State University of Maring\u00e1, Maring\u00e1 (UEM), Maring\u00e1, Paran\u00e1 87020-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patr\u00edcia de Souza","family":"Bonfim-Mendon\u00e7a","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Mycology, Department of Clinical Analysis and Biomedicine, State University of Maring\u00e1 (UEM), Maring\u00e1, Paran\u00e1 87020-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Sueli Soares","family":"Felipe","sequence":"additional","affiliation":[{"name":"Program of Genomic Sciences and Biotechnology, Catholic University of Brasilia, Bras\u00edlia 70790-160, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2525-9046","authenticated-orcid":false,"given":"Terezinha Inez Estivalet","family":"Svidzinski","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Mycology, Department of Clinical Analysis and Biomedicine, State University of Maring\u00e1 (UEM), Maring\u00e1, Paran\u00e1 87020-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3290-8577","authenticated-orcid":false,"given":"Erika Seki","family":"Kioshima","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Mycology, Department of Clinical Analysis and Biomedicine, State University of Maring\u00e1 (UEM), Maring\u00e1, Paran\u00e1 87020-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1111\/tid.12356","article-title":"Nosocomial bloodstream infections in a nationwide study: Comparison between solid organ transplant patients and the general population","volume":"17","author":"Camargo","year":"2015","journal-title":"Transpl. Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.jhin.2018.03.003","article-title":"Multi-hospital point prevalence study of healthcare-associated infections in 28 adult intensive care units in Brazil","volume":"99","author":"Braga","year":"2018","journal-title":"J. Hosp. Infect."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ortega-Loubon, C., Cano-Hern\u00e1ndez, B., Poves-Alvarez, R., Mu\u00f1oz-Moreno, M.F., Rom\u00e1n-Garc\u00eda, P., Balb\u00e1s-Alvarez, S., de la Varga-Mart\u00ednez, O., G\u00f3mez-S\u00e1nchez, E., G\u00f3mez-Pesquera, E., and Lorenzo-L\u00f3pez, M. (2019). The Overlooked Immune State in Candidemia: A Risk Factor for Mortality. J. Clin. Med., 8.","DOI":"10.3390\/jcm8101512"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/s13613-019-0539-2","article-title":"Candidemia in critically ill immunocompromised patients: Report of a retrospective multicenter cohort study","volume":"9","author":"Ghrenassia","year":"2019","journal-title":"Ann. Intensive Care"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/1469-0691.12539","article-title":"Global trends in the distribution of Candida species causing candidemia","volume":"20","author":"Guinea","year":"2014","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_6","unstructured":"Cort\u00e9s, J.A., and Corrales, I.F. (2018). Invasive candidiasis: Epidemiology and risk factors. Fungal Infection, InTechOpen."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1080\/23744235.2017.1384956","article-title":"The role of biofilm forming on mortality in patients with candidemia: A study derived from real world data","volume":"50","author":"Tascini","year":"2018","journal-title":"Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e37385","DOI":"10.5812\/jjm.37385","article-title":"Resistance of Candida albicans biofilms to drugs and the host immune system","volume":"9","author":"Sandai","year":"2016","journal-title":"Jundishapur J. Microbiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1093\/cid\/civ933","article-title":"Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America","volume":"62","author":"Pappas","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_10","first-page":"271","article-title":"Invasive fungal infection","volume":"116","author":"Wagener","year":"2019","journal-title":"Dtsch. Arztebl. Int."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.riam.2009.06.003","article-title":"Amphotericin B: Side effects and toxicity","volume":"26","year":"2009","journal-title":"Rev. Iberoam. Micol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1086\/598327","article-title":"Clinical relevance of the pharmacokinetic interactions of azole antifungal drugs with other coadministered agents","volume":"48","author":"Alffenaar","year":"2009","journal-title":"Clin. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2173","DOI":"10.3389\/fmicb.2016.02173","article-title":"Azole antifungal resistance in Candida albicans and emerging non-albicans Candida species","volume":"7","author":"Whaley","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e00906","DOI":"10.1128\/AAC.00906-17","article-title":"Monitoring antifungal resistance in a global collection of invasive yeasts and molds: Application of CLSI epidemiological cutoff values and whole-genome sequencing analysis for detection of azole resistance in Candida albicans","volume":"61","author":"Castanheira","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"451","DOI":"10.14740\/jocmr2992w","article-title":"Combination antifungal therapy: A review of current data","volume":"9","author":"Campitelli","year":"2017","journal-title":"J. Clin. Med. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"36","DOI":"10.3389\/fmicb.2017.00036","article-title":"Antifungal therapy: New advances in the understanding and treatment of mycosis","volume":"8","author":"Scorzoni","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Batool, M., Ahmad, B., and Choi, S. (2019). A structure-based drug discovery paradigm. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20112783"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Mariappan, G., and Kumari, A. (2019). Virtual screening and its applications in drug discovery process. Computer Applications in Drug Discovery and Development, IGI Global.","DOI":"10.4018\/978-1-5225-7326-5.ch005"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"6102","DOI":"10.1046\/j.1432-1327.2000.01701.x","article-title":"Physiological functions of thioredoxin and thioredoxin reductase","volume":"267","author":"Holmgren","year":"2000","journal-title":"Eur. J. Biochem."},{"key":"ref_20","unstructured":"Kioshima, E.S., Svidzinski, T.I., Bonfim-Mendon\u00e7a, P.S., Capoci, I.R., Faria, D.R., Sakita, K.M., Morelli, F., Rodrigues, F.A., Felipe, M.S., and Chaucan\u00e9s, C.P. (2018). Composi\u00e7\u00e3o Farmac\u00eautica Baseada em Compostos 1,3,4-Oxadiaz\u00f3licos e Seu Uso na Prepara\u00e7\u00e3o de Medicamentos para Tratamento de Infec\u00e7\u00f5es Sist\u00eamicas. (BR 10 2018 009020 8), Brazil Patent."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Rodrigues-Vendramini, F.A., Faria, D.R., Arita, G.S., Capoci, I.R., Sakita, K.M., Caparroz-Assef, S.M., Becker, T., Bonfim-Mendon\u00e7a, P.S., Felipe, M.S., and Svidzinski, T.I. (2019). Antifungal activity of two oxadiazole compounds for the paracoccidioidomycosis treatment. PLoS Negl. Trop. Dis., 13.","DOI":"10.1371\/journal.pntd.0007441"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2130","DOI":"10.3389\/fmicb.2019.02130","article-title":"Two new 1,3,4-oxadiazoles with effective antifungal activity against Candida albicans","volume":"10","author":"Capoci","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Faria, D.R., Sakita, K.M., Capoci, I.R., Arita, G.S., Rodrigues-Vendramini, F.A., de Oliveira Junior, A.G., Felipe, M.S., Bonfim-Mendon\u00e7a, P.S., Svidzinski, T.I., and Kioshima, E.S. (2020). Promising antifungal activity of new oxadiazole against Candida krusei. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0227876"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.bcp.2016.11.019","article-title":"Antifungals","volume":"133","author":"Campoy","year":"2017","journal-title":"Biochem. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Abadio, A.K., Kioshima, E.S., Leroux, V., Martins, N.F., Maigret, B., and Felipe, M.S. (2015). Identification of new antifungal compounds targeting thioredoxin reductase of Paracoccidioides genus. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0142926"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"21","DOI":"10.2174\/1570180814666170425160545","article-title":"New oxadiazole derivatives: Synthesis and appraisal of their potential as antimicrobial agents","volume":"15","author":"Dhara","year":"2018","journal-title":"Lett. Drug. Des. Discov."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.ejmech.2017.12.020","article-title":"The synthesis, antifungal and apoptotic effects of triazole-oxadiazoles against Candida species","volume":"144","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Karaburun, A.\u00c7., \u00c7avu\u015fo\u011flu, B.K., \u00c7evik, U.A., Osmaniye, D., Sa\u011fl\u0131k, B.N., Levent, S., \u00d6zkay, Y., Atl\u0131, \u00d6., Koparal, A.S., and Kaplanc\u0131kl\u0131, Z.A. (2019). Synthesis and antifungal potential of some novel benzimidazole-1,3,4-oxadiazole compounds. Molecules, 24.","DOI":"10.3390\/molecules24010191"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"477","DOI":"10.2174\/1389557518666181015152433","article-title":"A review exploring therapeutic worth of 1,3,4-oxadiazole tailored compounds","volume":"19","author":"Verma","year":"2019","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1080\/21501203.2017.1421592","article-title":"Fungicidal versus fungistatic therapy of invasive Candida infection in non-neutropenic adults: A meta-analysis","volume":"9","author":"Kumar","year":"2018","journal-title":"Mycology"},{"key":"ref_31","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\u2013activity relationship study","volume":"25","author":"Barbero","year":"2016","journal-title":"Med. Chem. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.3389\/fmicb.2018.01196","article-title":"The impact of biofilm formation on the persistence of candidemia","volume":"9","author":"Li","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1093\/mmy\/myv052","article-title":"Effect of tyrosol on adhesion of Candida albicans and Candida glabrata to acrylic surfaces","volume":"53","author":"Monteiro","year":"2015","journal-title":"Med. Mycol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1111\/j.1469-0691.2008.01983.x","article-title":"Combination antifungal therapy: A critical review of the evidence","volume":"14","year":"2008","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1093\/jac\/dkg230","article-title":"Efficacy of caspofungin combined with amphotericin B against azole-resistant Candida albicans","volume":"51","author":"Hossain","year":"2003","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.phymed.2017.12.033","article-title":"Caffeic acid phenethyl ester synergistically enhances the antifungal activity of fluconazole against resistant Candida albicans","volume":"40","author":"Sun","year":"2018","journal-title":"Phytomedicine"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.3389\/fmicb.2019.02071","article-title":"The synergism of the small molecule ENOblock and fluconazole against fluconazole-resistant Candida albicans","volume":"10","author":"Li","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Khalifa, H.O., Majima, H., Watanabe, A., and Kamei, K. (2021). In Vitro Characterization of Twenty-One Antifungal Combinations against Echinocandin-Resistant and -Susceptible Candida glabrata. J. Fungi, 7.","DOI":"10.3390\/jof7020108"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"108896","DOI":"10.1016\/j.cbi.2019.108896","article-title":"Preclinical toxicity of innovative molecules: In vitro, in vivo and metabolism prediction","volume":"315","author":"Tonholo","year":"2020","journal-title":"Chem. Biol. Interact."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.jep.2019.02.026","article-title":"Acute and sub-acute toxicity of the aqueous extract from the stem bark of Tetrapleura tetrapteura Taub. (Fabaceae) in mice and rats","volume":"236","author":"Dongmo","year":"2019","journal-title":"J. Ethnopharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1080\/01926230701595300","article-title":"Society of Toxicologic Pathology position paper: Organ weight recommendations for toxicology studies","volume":"35","author":"Sellers","year":"2007","journal-title":"Toxicol. Pathol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"556","DOI":"10.2174\/1389200218666170316093301","article-title":"Drug metabolism in preclinical drug development: A survey of the discovery process, toxicology, and computational tools","volume":"18","author":"Issa","year":"2017","journal-title":"Curr. Drug Metab."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.cll.2010.10.004","article-title":"Preclinical safety assessment: Current gaps, challenges, and approaches in identifying translatable biomarkers of drug-induced liver injury","volume":"31","author":"Ramaiah","year":"2011","journal-title":"Clin. Lab. Med."},{"key":"ref_44","first-page":"457","article-title":"Drug-induced impairment of renal function","volume":"7","author":"Pazhayattil","year":"2014","journal-title":"Int. J. Nephrol. Renovasc. Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e19","DOI":"10.1309\/LM920SBNZPJRJGUT","article-title":"Overview of urea and creatinine","volume":"45","author":"Salazar","year":"2014","journal-title":"Lab. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1016\/S0140-6736(19)32563-2","article-title":"Acute kidney injury","volume":"394","author":"Ronco","year":"2019","journal-title":"Lancet"},{"key":"ref_47","first-page":"236","article-title":"Hematological markers of in vivo toxicity","volume":"4","author":"Arika","year":"2016","journal-title":"J. Hematol. Thrombo. Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"138","DOI":"10.11606\/issn.1678-4456.v53i2p138-145","article-title":"Hematological and biochemical reference values for C57BL\/6, Swiss Webster and BALB\/c mice","volume":"53","author":"Santos","year":"2016","journal-title":"Braz. J. Vet. Res. Anim. Sci."},{"key":"ref_49","first-page":"1477","article-title":"Haematological and biochemical profile of Balb-c mice","volume":"45","author":"Barbosa","year":"2017","journal-title":"Acta Sci. Vet."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1086\/430952","article-title":"Mice with disseminated candidiasis die of progressive sepsis","volume":"192","author":"Spellberg","year":"2005","journal-title":"J. Infect. Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1159\/000321157","article-title":"Organ-specific innate immune responses in a mouse model of invasive candidiasis","volume":"3","author":"Lionakis","year":"2011","journal-title":"J. Innate Immun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"179","DOI":"10.3892\/br.2014.393","article-title":"Mechanism underlying renal failure caused by pathogenic Candida albicans infection","volume":"3","author":"Seok","year":"2015","journal-title":"Biomed. Rep."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"18026","DOI":"10.1038\/nrdp.2018.26","article-title":"Invasive candidiasis","volume":"4","author":"Pappas","year":"2018","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1111\/j.1365-2141.2005.05498.x","article-title":"Cytokines and fungal infections","volume":"129","author":"Antachopoulos","year":"2005","journal-title":"Br. J. Haematol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"16905","DOI":"10.1038\/s41598-019-53402-z","article-title":"Rhesus theta defensin 1 promotes long term survival in systemic candidiasis by host directed mechanisms","volume":"9","author":"Basso","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Yarrow, D. (1998). Methods for the isolation, maintenance and identification of yeasts. The Yeasts, A Taxonomic Study, Elsevier.","DOI":"10.1016\/B978-044481312-1\/50014-9"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1111\/myc.12506","article-title":"Performance of MALDI-TOF MS platforms for fungal identification","volume":"59","author":"Cassagne","year":"2016","journal-title":"Mycoses"},{"key":"ref_58","unstructured":"CLSI (2008). Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts, Clinical and Laboratory Standards Institute. [3rd ed.]. CLSI Document M27-A3."},{"key":"ref_59","unstructured":"CLSI (2012). Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts, Clinical and Laboratory Standards Institute. CLSI Document M27-S4."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1128\/AAC.41.6.1392","article-title":"Antifungal pharmacodynamic characteristics of fluconazole and amphotericin B tested against Candida albicans","volume":"41","author":"Klepser","year":"1997","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e01961-16","DOI":"10.1128\/AAC.01961-16","article-title":"SCY-078 is fungicidal against Candida species in time-kill studies","volume":"61","author":"Scorneaux","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"33","DOI":"10.3109\/13693786.2011.582890","article-title":"Anti-candidal activity of essential oils alone and in combination with amphotericin B or fluconazole against multi-drug resistant isolates of Candida albicans","volume":"50","author":"Khan","year":"2012","journal-title":"Med. Mycol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e00647-15","DOI":"10.1128\/mBio.00647-15","article-title":"Identification of a new class of antifungals targeting the synthesis of fungal sphingolipids","volume":"6","author":"Mor","year":"2015","journal-title":"mBio"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2866","DOI":"10.1093\/bioinformatics\/btw230","article-title":"Combenefit: An interactive platform for the analysis and visualization of drug combinations","volume":"32","author":"Fornari","year":"2016","journal-title":"Bioinformatics"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.2217\/fmb-2015-0016","article-title":"Propolis: A potential natural product to fight Candida species infections","volume":"11","author":"Rosseto","year":"2016","journal-title":"Future Microbiol."},{"key":"ref_66","first-page":"113","article-title":"Bioactive organocopper compound from Pseudomonas aeruginosa inhibits the growth of Xanthomonas citri subsp","volume":"7","author":"Spago","year":"2016","journal-title":"citri. Front. Microbiol."},{"key":"ref_67","unstructured":"Ag\u00eancia Nacional de Vigil\u00e2ncia Sanit\u00e1ria (ANVISA) (2020, February 05). Guia Para a Condu\u00e7\u00e3o de Estudos n\u00e3o Cl\u00ednicos de Toxicologia e Seguran\u00e7a Farmacol\u00f3gica Necess\u00e1rios ao Desenvolvimento de Medicamentos, Available online: https:\/\/bit.ly\/2OA6uWr."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.joad.2015.06.010","article-title":"Evaluation of the acute and sub-acute toxicity of the ethanolic extract of Pericampylus glaucus (Lam.) Merr. in BALB\/c mice","volume":"4","author":"Kifayatullah","year":"2015","journal-title":"J. Acute. Dis."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Briggs, C., and Bain, B.J. (2017). Basic haematological techniques. Dacie and Lewis Practical Haematology, Elsevier.","DOI":"10.1016\/B978-0-7020-6696-2.00003-5"},{"key":"ref_70","unstructured":"Araujo, A.V. (2017). Estudos Pr\u00e9-Cl\u00ednicos de Toxicidade Aguda e de Doses Repetidas da Fosfoetanolamina Sint\u00e9tica. [Master\u2032s Thesis, Universidade de S\u00e3o Paulo]. Available online: https:\/\/www.teses.usp.br\/teses\/disponiveis\/5\/5160\/tde-15032018-092543\/publico\/AlineVieiraPinheiroDeAraujo.pdf."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1152\/jappl.1950.3.6.365","article-title":"Morphology and enumeration of human blood platelets","volume":"3","author":"Brecher","year":"1950","journal-title":"J. Appl. Physiol."},{"key":"ref_72","first-page":"141","article-title":"Determination of hemoglobin and its derivatives","volume":"8","author":"Zijlstra","year":"1965","journal-title":"Adv. Clin. Chem."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Wong, S.S., Kao, R.Y., Yuen, K.Y., Wang, Y., Yang, D., Samaranayake, L.P., and Seneviratne, C.J. (2014). In vitro and in vivo activity of a novel antifungal small molecule against Candida infections. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0085836"}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/10\/3\/314\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:34:36Z","timestamp":1760160876000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/10\/3\/314"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,7]]},"references-count":73,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["pathogens10030314"],"URL":"https:\/\/doi.org\/10.3390\/pathogens10030314","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,7]]}}}