{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T11:22:06Z","timestamp":1762082526878,"version":"build-2065373602"},"reference-count":44,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,31]],"date-time":"2022-12-31T00:00:00Z","timestamp":1672444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"MCTI\/CNPq (Minist\u00e9rio da Ci\u00eancia e Tecnologia\/Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico-)","doi-asserted-by":"publisher","award":["404455\/2016-6"],"award-info":[{"award-number":["404455\/2016-6"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"name":"FNDCT (Fundo Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico)","award":["404455\/2016-6"],"award-info":[{"award-number":["404455\/2016-6"]}]},{"name":"FAPEG (Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de Goi\u00e1s)","award":["404455\/2016-6"],"award-info":[{"award-number":["404455\/2016-6"]}]},{"name":"CAPES (Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior\/Finance Code 001)","award":["404455\/2016-6"],"award-info":[{"award-number":["404455\/2016-6"]}]},{"name":"FINEP (Financiadora de Estudos e Projetos)","award":["404455\/2016-6"],"award-info":[{"award-number":["404455\/2016-6"]}]},{"name":"PRONEX (Programa de Apoio a N\u00facleos de Excel\u00eancia)","award":["404455\/2016-6"],"award-info":[{"award-number":["404455\/2016-6"]}]},{"name":"INCT-IPH (Instituto Nacional de Ci\u00eancia e Tecnologia de Estrat\u00e9gias de Intera\u00e7\u00e3o Pat\u00f3geno-Hospedeiro)","award":["404455\/2016-6"],"award-info":[{"award-number":["404455\/2016-6"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>Background: Paracoccidioidomycosis is a neglected mycosis with a high socioeconomic impact that requires long-term treatment with antifungals that have limitations in their use. The development of antifungals targeting essential proteins that are present exclusively in the fungus points to a potentially promising treatment. Methods: The inhibitor of the enzyme homoserine dehydrogenase drove the synthesis of N\u2019-(2-hydroxybenzylidene)-4-methoxy-1-naphthohydrazide (AOS). This compound was evaluated for its antifungal activity in different species of Paracoccidioides and the consequent alteration in the proteomic profile of Paracoccidioides brasiliensis. Results: The compound showed a minimal inhibitory concentration ranging from 0.75 to 6.9 \u03bcM with a fungicidal effect on Paracoccidioides spp. and high selectivity index. AOS differentially regulated proteins related to glycolysis, TCA, the glyoxylate cycle, the urea cycle and amino acid metabolism, including homoserine dehydrogenase. In addition, P. brasiliensis inhibited protein synthesis and stimulated reactive oxygen species in the presence of AOS. Conclusions: AOS is a promising antifungal agent for the treatment of PCM, targeting important metabolic processes of the fungus.<\/jats:p>","DOI":"10.3390\/jof9010066","type":"journal-article","created":{"date-parts":[[2023,1,2]],"date-time":"2023-01-02T04:07:09Z","timestamp":1672632429000},"page":"66","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Proteomic Response of Paracoccidioides brasiliensis Exposed to the Antifungal 4-Methoxynaphthalene-N-acylhydrazone Reveals Alteration in Metabolism"],"prefix":"10.3390","volume":"9","author":[{"given":"L\u00edvia do Carmo","family":"Silva","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Biology, Institute of Biological Sciences, Federal University of Goi\u00e1s, Goi\u00e1s 74690-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5350-7313","authenticated-orcid":false,"given":"Kleber Santiago Freitas e","family":"Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Institute of Biological Sciences, Federal University of Goi\u00e1s, Goi\u00e1s 74690-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2094-6042","authenticated-orcid":false,"given":"Ol\u00edvia Basso","family":"Rocha","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Institute of Biological Sciences, Federal University of Goi\u00e1s, Goi\u00e1s 74690-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katheryne Lohany Barros","family":"Barbosa","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Institute of Biological Sciences, Federal University of Goi\u00e1s, Goi\u00e1s 74690-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew Matheus Frederico","family":"Rozada","sequence":"additional","affiliation":[{"name":"Department of Chemistry, State University of Maringa, Paran\u00e1 87020-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gisele de Freitas","family":"Gauze","sequence":"additional","affiliation":[{"name":"Department of Chemistry, State University of Maringa, Paran\u00e1 87020-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5378-9840","authenticated-orcid":false,"given":"C\u00e9lia Maria de Almeida","family":"Soares","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Institute of Biological Sciences, Federal University of Goi\u00e1s, Goi\u00e1s 74690-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5482-8036","authenticated-orcid":false,"given":"Maristela","family":"Pereira","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Institute of Biological Sciences, Federal University of Goi\u00e1s, Goi\u00e1s 74690-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1590\/0037-8682-0230-2017","article-title":"Brazilian Guidelines for the Clinical Management of Paracoccidioidomycosis","volume":"50","author":"Mendes","year":"2017","journal-title":"Rev. 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