{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T07:17:28Z","timestamp":1774336648728,"version":"3.50.1"},"reference-count":68,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,8]],"date-time":"2021-10-08T00:00:00Z","timestamp":1633651200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Histoplasma capsulatum is a dimorphic fungal pathogen endemic to the midwestern and southern United States. It causes mycoses ranging from subclinical respiratory infections to severe systemic disease, and is of particular concern for immunocompromised patients in endemic areas. Clinical management of histoplasmosis relies on protracted regimens of antifungal drugs whose effectiveness can be limited by toxicity. In this study, we hypothesize that conserved biochemical signaling pathways in the eukaryotic domain can be leveraged to repurpose kinase inhibitors as antifungal compounds. We conducted a screen of two kinase inhibitor libraries to identify compounds inhibiting the growth of Histoplasma capsulatum in the pathogenic yeast form. Our approach identified seven compounds with an elongated hydrophobic polyaromatic structure, five of which share a molecular motif including a urea unit linking a halogenated benzene ring and a para-substituted polyaromatic group. The top hits include the cancer therapeutic Sorafenib, which inhibits growth of Histoplasma in vitro and in a macrophage infection model with low host cell cytotoxicity. Our results reveal the possibility of repurposing Sorafenib or derivatives thereof as therapy for histoplasmosis, and suggest that repurposing of libraries developed for human cellular targets may be a fruitful source of antifungal discovery.<\/jats:p>","DOI":"10.3390\/antibiotics10101223","type":"journal-article","created":{"date-parts":[[2021,10,9]],"date-time":"2021-10-09T23:37:08Z","timestamp":1633822628000},"page":"1223","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Kinase Inhibitor Library Screening Identifies the Cancer Therapeutic Sorafenib and Structurally Similar Compounds as Strong Inhibitors of the Fungal Pathogen Histoplasma capsulatum"],"prefix":"10.3390","volume":"10","author":[{"given":"Charlotte","family":"Berkes","sequence":"first","affiliation":[{"name":"Department of Biology, Merrimack College, North Andover, MA 01845, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9085-1356","authenticated-orcid":false,"given":"Jimmy","family":"Franco","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Merrimack College, North Andover, MA 01845, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maxx","family":"Lawson","sequence":"additional","affiliation":[{"name":"Department of Biology, Merrimack College, North Andover, MA 01845, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katelynn","family":"Brann","sequence":"additional","affiliation":[{"name":"Department of Biology, Merrimack College, North Andover, MA 01845, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Mermelstein","sequence":"additional","affiliation":[{"name":"Department of Biology, Merrimack College, North Andover, MA 01845, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Laverty","sequence":"additional","affiliation":[{"name":"Department of Biology, Merrimack College, North Andover, MA 01845, USA"},{"name":"Department of Chemistry and Biochemistry, Merrimack College, North Andover, MA 01845, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allison","family":"Connors","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Merrimack College, North Andover, MA 01845, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3109\/10408410903241444","article-title":"Epidemiology of Invasive Mycoses in North America","volume":"36","author":"Pfaller","year":"2010","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1093\/cid\/ciy776","article-title":"Estimation of Direct Healthcare Costs of Fungal Diseases in the United States","volume":"68","author":"Benedict","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"967","DOI":"10.2217\/fmb.15.25","article-title":"Histoplasma capsulatum, lung infection and immunity","volume":"10","author":"Horwath","year":"2015","journal-title":"Futur. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1016\/j.rmed.2005.09.020","article-title":"Reactivation histoplasmosis after treatment with anti-tumor necrosis factor \u03b1 in a patient from a nonendemic area","volume":"100","author":"Jain","year":"2006","journal-title":"Respir. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1093\/cid\/civ299","article-title":"Histoplasmosis Complicating Tumor Necrosis Factor\u2013\u03b1 Blocker Therapy: A Retrospective Analysis of 98 Cases","volume":"61","author":"Vergidis","year":"2015","journal-title":"Clin. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/S0002-9343(01)00945-7","article-title":"Reactivation of histoplasmosis after treatment with infliximab","volume":"112","author":"Nakelchik","year":"2002","journal-title":"Am. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e005170","DOI":"10.1099\/jmmcr.0.005170","article-title":"Reactivation of latent Histoplasma and disseminated cytomegalovirus in a returning traveller with ulcerative colitis","volume":"5","author":"Lucey","year":"2018","journal-title":"JMM Case Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/nrd.2017.46","article-title":"The antifungal pipeline: A reality check","volume":"16","author":"Perfect","year":"2017","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/S0966-842X(03)00117-3","article-title":"Antifungal agents: Mechanisms of action","volume":"11","author":"Odds","year":"2003","journal-title":"Trends Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1086\/521259","article-title":"Clinical Practice Guidelines for the Management of Patients with Histoplasmosis: 2007 Update by the Infectious Diseases Society of America","volume":"45","author":"Wheat","year":"2007","journal-title":"Clin. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.idc.2015.10.012","article-title":"Antifungal Agents: Spectrum of Activity, Pharmacology, and Clinical Indications","volume":"30","author":"Nett","year":"2016","journal-title":"Infect. Dis. Clin. North Am."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1086\/319211","article-title":"Mortality and Costs of Acute Renal Failure Associated with Amphotericin B Therapy","volume":"32","author":"Bates","year":"2001","journal-title":"Clin. Infect. Dis."},{"key":"ref_13","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_14","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1128\/AAC.47.4.1376-1381.2003","article-title":"In Vitro Antifungal Activity of Micafungin (FK463) against Dimorphic Fungi: Comparison of Yeast-Like and Mycelial Forms","volume":"47","author":"Nakai","year":"2003","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4447","DOI":"10.1128\/AAC.01681-10","article-title":"Investigation of the Efficacy of Micafungin in the Treatment of Histoplasmosis Using Two North American Strains of Histoplasma capsulatum","volume":"55","author":"Hage","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"a019703","DOI":"10.1101\/cshperspect.a019703","article-title":"Antifungal Drug Development: Challenges, Unmet Clinical Needs, and New Approaches","volume":"4","author":"Roemer","year":"2014","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/nrd.2018.168","article-title":"Drug repurposing: Progress, challenges and recommendations","volume":"18","author":"Pushpakom","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1517\/17460441.2012.724056","article-title":"System-based drug discovery within the human kinome","volume":"7","author":"Bamborough","year":"2012","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.tips.2015.04.005","article-title":"FDA-approved small-molecule kinase inhibitors","volume":"36","author":"Wu","year":"2015","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1038\/nchembio0709-436","article-title":"Open access chemical and clinical probes to support drug discovery","volume":"5","author":"Edwards","year":"2009","journal-title":"Nat. Chem. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1128\/MMBR.66.2.300-372.2002","article-title":"Osmotic Stress Signaling and Osmoadaptation in Yeasts","volume":"66","author":"Hohmann","year":"2002","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1242\/jcs.113.3.507","article-title":"Type 1 protein phosphatase is required for maintenance of cell wall integrity, morphogenesis and cell cycle progression in Saccharomyces cerevisiae","volume":"113","author":"Andrews","year":"2000","journal-title":"J. Cell Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1128\/MMBR.62.4.1264-1300.1998","article-title":"MAP Kinase Pathways in the Yeast Saccharomyces cerevisiae","volume":"62","author":"Gustin","year":"1998","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1126\/science.276.5319.1702","article-title":"Osmotic Activation of the HOG MAPK Pathway via Ste11p MAPKKK: Scaffold Role of Pbs2p MAPKK","volume":"276","author":"Posas","year":"1997","journal-title":"Science"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1099\/mic.0.26110-0","article-title":"Response to high osmotic conditions and elevated temperature in Saccharomyces cerevisiae is controlled by intracellular glycerol and involves coordinate activity of MAP kinase pathways","volume":"149","author":"Wojda","year":"2003","journal-title":"Microbiology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1046\/j.1365-2958.2001.02672.x","article-title":"Ras links cellular morphogenesis to virulence by regulation of the MAP kinase and cAMP signalling pathways in the pathogenic fungus Candida albicans","volume":"42","author":"Leberer","year":"2008","journal-title":"Mol. Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2539","DOI":"10.1091\/mbc.8.12.2539","article-title":"Derepressed Hyphal Growth and Reduced Virulence in a VH1 Family-related Protein Phosphatase Mutant of the Human Pathogen Candida albicans","volume":"8","author":"Csank","year":"1997","journal-title":"Mol. Biol. Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1111\/j.1567-1364.2010.00626.x","article-title":"The MAP kinase-activated protein kinase Rck2p regulates cellular responses to cell wall stresses, filamentation and virulence in the human fungal pathogen Candida albicans","volume":"10","author":"Li","year":"2010","journal-title":"FEMS Yeast Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"12766","DOI":"10.1038\/ncomms12766","article-title":"Systematic functional analysis of kinases in the fungal pathogen Cryptococcus neoformans","volume":"7","author":"Lee","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2285","DOI":"10.1091\/mbc.e04-11-0987","article-title":"Specialization of the HOG Pathway and Its Impact on Differentiation and Virulence of Cryptococcus neoformans","volume":"16","author":"Bahn","year":"2005","journal-title":"Mol. Biol. Cell"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Kim, S.-Y., Ko, Y.-J., Jung, K.-W., Strain, A., Nielsen, K., and Bahn, Y.-S. (2011). Hrk1 Plays Both Hog1-Dependent and -Independent Roles in Controlling Stress Response and Antifungal Drug Resistance in Cryptococcus neoformans. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0018769"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/S0968-0004(02)02179-5","article-title":"Evolution of protein kinase signaling from yeast to man","volume":"27","author":"Manning","year":"2002","journal-title":"Trends Biochem. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1099\/mic.0.28571-0","article-title":"Calcineurin, Mpk1 and Hog1 MAPK pathways independently control fludioxonil antifungal sensitivity in Cryptococcus neoformans","volume":"152","author":"Kojima","year":"2006","journal-title":"Microbiology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/nbt.3374","article-title":"Comprehensive characterization of the Published Kinase Inhibitor Set","volume":"34","author":"Elkins","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"340","DOI":"10.2174\/1568026613666131127160819","article-title":"Seeding Collaborations to Advance Kinase Science with the GSK Published Kinase Inhibitor Set (PKIS)","volume":"14","author":"Drewry","year":"2014","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4349","DOI":"10.1128\/AAC.00459-13","article-title":"Identification of an Aminothiazole with Antifungal Activity against Intracellular Histoplasma capsulatum","volume":"57","author":"Edwards","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3286","DOI":"10.1128\/JCM.00795-15","article-title":"Quantitative Microplate-Based Growth Assay for Determination of Antifungal Susceptibility of Histoplasma capsulatum Yeasts","volume":"53","author":"Goughenour","year":"2015","journal-title":"J. Clin. Microbiol."},{"key":"ref_38","unstructured":"Silverman, R.B., and Holladay, M.W. (2014). The Organic Chemistry of Drug Design and Drug Action. The Organic Chemistry of Drug Design and Drug Action, Academic Press. [3rd ed.]."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.addr.2012.09.019","article-title":"Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings","volume":"64","author":"Lipinski","year":"2012","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1021\/cc9800071","article-title":"A Knowledge-Based Approach in Designing Combinatorial or Medicinal Chemistry Libraries for Drug Discovery. 1. A Qualitative and Quantitative Characterization of Known Drug Databases","volume":"1","author":"Ghose","year":"1999","journal-title":"J. Comb. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1016\/j.jhep.2011.01.047","article-title":"Signal transducer and activator of transcription 3 is a major kinase-independent target of sorafenib in hepatocellular carcinoma","volume":"55","author":"Tai","year":"2011","journal-title":"J. Hepatol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.2147\/OTT.S161534","article-title":"Synergistic antitumor effects of tanshinone IIA and sorafenib or its derivative SC-1 in hepatocellular carcinoma cells","volume":"11","author":"Chiu","year":"2018","journal-title":"OncoTargets Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"7243","DOI":"10.1073\/pnas.1507499112","article-title":"Sorafenib and its derivative SC-1 exhibit antifibrotic effects through signal transducer and activator of transcription 3 inhibition","volume":"112","author":"Su","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1111\/mmi.13168","article-title":"Macrophage cell death and transcriptional response are actively triggered by the fungal virulence factor Cbp1 during H.capsulatum infection","volume":"98","author":"Isaac","year":"2015","journal-title":"Mol. Microbiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1039\/C4MD00045E","article-title":"Repurposing human Aurora kinase inhibitors as leads for anti-protozoan drug discovery","volume":"5","author":"Patel","year":"2014","journal-title":"MedChemComm"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1002\/cmdc.201700259","article-title":"Repurposing of Human Kinase Inhibitors in Neglected Protozoan Diseases","volume":"12","author":"Dichiara","year":"2017","journal-title":"ChemMedChem"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1128\/AAC.01087-13","article-title":"Antifungal Application of Nonantifungal Drugs","volume":"58","author":"Stylianou","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1128\/EC.00314-12","article-title":"A Repurposing Approach Identifies Off-Patent Drugs with Fungicidal Cryptococcal Activity, a Common Structural Chemotype, and Pharmacological Properties Relevant to the Treatment of Cryptococcosis","volume":"12","author":"Butts","year":"2012","journal-title":"Eukaryot. Cell"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1016\/j.bmc.2014.12.006","article-title":"Design, synthesis, and biological evaluation of aminothiazole derivatives against the fungal pathogens Histoplasma capsulatum and Cryptococcus neoformans","volume":"23","author":"Khalil","year":"2015","journal-title":"Bioorganic Med. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Catalano, A., Iacopetta, D., Sinicropi, M.S., and Franchini, C. (2021). Diarylureas as Antitumor Agents. Appl. Sci., 11.","DOI":"10.3390\/app11010374"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.2174\/0929867323666160411142532","article-title":"Diaryl Urea: A Privileged Structure in Anticancer Agents","volume":"23","author":"Garuti","year":"2016","journal-title":"Curr. Med. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Catalano, A., Iacopetta, D., Pellegrino, M., Aquaro, S., Franchini, C., and Sinicropi, M. (2021). Diarylureas: Repositioning from Antitumor to Antimicrobials or Multi-Target Agents against New Pandemics. Antibiotics, 10.","DOI":"10.3390\/antibiotics10010092"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Iacopetta, D., Catalano, A., Ceramella, J., Saturnino, C., Salvagno, L., Ielo, I., Drommi, D., Scali, E., Plutino, M., and Rosace, G. (2021). The Different Facets of Triclocarban: A Review. Molecules, 26.","DOI":"10.3390\/molecules26092811"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Catalano, A., Rosato, A., Salvagno, L., Iacopetta, D., Ceramella, J., Fracchiolla, G., Sinicropi, M., and Franchini, C. (2021). Benzothiazole-Containing Analogues of Triclocarban with Potent Antibacterial Activity. Antibiotics, 10.","DOI":"10.3390\/antibiotics10070803"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.antiviral.2018.07.005","article-title":"Repurposed FDA-Approved drug sorafenib reduces replication of Venezuelan equine encephalitis virus and other alphaviruses","volume":"157","author":"Lundberg","year":"2018","journal-title":"Antivir. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3562","DOI":"10.3390\/molecules18033562","article-title":"Synthesis and Biological Activity of Substituted Urea and Thiourea Derivatives Containing 1,2,4-Triazole Moieties","volume":"18","author":"Celen","year":"2013","journal-title":"Molecules"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2862","DOI":"10.1128\/AAC.43.12.2862","article-title":"Comparison of In Vitro Activities of Camptothecin and Nitidine Derivatives against Fungal and Cancer Cells","volume":"43","author":"Chen","year":"1999","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1126\/science.1715094","article-title":"Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast","volume":"253","author":"Heitman","year":"1991","journal-title":"Science"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"27671","DOI":"10.1074\/jbc.272.44.27671","article-title":"STT4 Is an Essential Phosphatidylinositol 4-Kinase That Is a Target of Wortmannin in Saccharomyces cerevisiae","volume":"272","author":"Cutler","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"11851","DOI":"10.1158\/0008-5472.CAN-06-1377","article-title":"Sorafenib Blocks the RAF\/MEK\/ERK Pathway, Inhibits Tumor Angiogenesis, and Induces Tumor Cell Apoptosis in Hepatocellular Carcinoma Model PLC\/PRF\/5","volume":"66","author":"Liu","year":"2006","journal-title":"Cancer Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1158\/1535-7163.MCT-12-0093","article-title":"Sorafenib-Induced Hepatocellular Carcinoma Cell Death Depends on Reactive Oxygen Species Production In Vitro and In Vivo","volume":"11","author":"Coriat","year":"2012","journal-title":"Mol. Cancer Ther."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"R63","DOI":"10.1186\/bcr3457","article-title":"Novel sorafenib analogues induce apoptosis through SHP-1 dependent STAT3 inactivation in human breast cancer cells","volume":"15","author":"Liu","year":"2013","journal-title":"Breast Cancer Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1128\/EC.00216-07","article-title":"Mitogen-Activated Protein Kinase Pathways and Fungal Pathogenesis","volume":"6","author":"Zhao","year":"2007","journal-title":"Eukaryot. Cell"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.7164\/antibiotics.53.1182","article-title":"On the Mechanism of Action of the Myxobacterial Fungicide Ambruticin","volume":"53","author":"Knauth","year":"2000","journal-title":"J. Antibiot."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1111\/j.1365-2958.2006.05436.x","article-title":"An \u03b1-(1,4)-amylase is essential for \u03b1 -(1,3)-glucan production and virulence in Histoplasma capsulatum","volume":"62","author":"Marion","year":"2006","journal-title":"Mol. Microbiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1128\/IAI.00833-12","article-title":"The 3-Hydroxy-Methylglutaryl Coenzyme a Lyase HCL1 Is Required for Macrophage Colonization by Human Fungal Pathogen Histoplasma capsulatum","volume":"81","author":"Isaac","year":"2013","journal-title":"Infect. Immun."},{"key":"ref_67","unstructured":"Rex, J.H., Alexander, B.D., Andes, D., Arthington-Skaggs, B., Brown, S.D., Chaturvedi, V., Ghannoum, M.A., Espinel-Ingroff, A., Knapp, C.C., and Ostrosky-Zeichner, L. (2008). Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts: Approved Standard, Clinical and Laboratory Standards Institute. [3rd ed.]."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2140","DOI":"10.1021\/ci700257y","article-title":"Computation of Octanol\u2212Water Partition Coefficients by Guiding an Additive Model with Knowledge","volume":"47","author":"Cheng","year":"2007","journal-title":"J. Chem. Inf. Model."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/10\/10\/1223\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:10:30Z","timestamp":1760166630000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/10\/10\/1223"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,8]]},"references-count":68,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["antibiotics10101223"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics10101223","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,8]]}}}