{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T16:36:24Z","timestamp":1790354184405,"version":"4.1.0"},"reference-count":56,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2017,9,1]],"date-time":"2017-09-01T00:00:00Z","timestamp":1504224000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Funda\u00e7\u00e3o Araucaria","award":["147\/14"],"award-info":[{"award-number":["147\/14"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            This work evaluated new potential inhibitors of the enzyme homoserine dehydrogenase (HSD) of\n            <jats:named-content content-type=\"genus-species\">Paracoccidioides brasiliensis<\/jats:named-content>\n            , one of the etiological agents of paracoccidioidomycosis. The tertiary structure of the protein bonded to the analogue NAD, and\n            <jats:sc>l<\/jats:sc>\n            -homoserine was modeled by homology. The model with the best output was subjected to gradient minimization, redocking, and molecular dynamics simulation. Virtual screening simulations with 187,841 molecules purchasable from the Zinc database were performed. After the screenings, 14 molecules were selected and analyzed by the use of absorption, distribution, metabolism, excretion, and toxicity criteria, resulting in four compounds for\n            <jats:italic>in vitro<\/jats:italic>\n            assays. The molecules HS1 and HS2 were promising, exhibiting MICs of 64 and 32 \u03bcg \u00b7 ml\n            <jats:sup>\u22121<\/jats:sup>\n            , respectively, for the Pb18 isolate of\n            <jats:named-content content-type=\"genus-species\">P. brasilensis<\/jats:named-content>\n            , 64 \u03bcg \u00b7 ml\n            <jats:sup>\u22121<\/jats:sup>\n            for two isolates of\n            <jats:named-content content-type=\"genus-species\">P. lutzii<\/jats:named-content>\n            , and also synergy with itraconazole. The application of these molecules to human-pathogenic fungi confirmed that the HSD enzyme may be used as a target for the development of drugs with specific action against paracoccidioidomycosis; moreover, these compounds may serve as leads in the design of new antifungals.\n          <\/jats:p>","DOI":"10.1128\/aac.00165-17","type":"journal-article","created":{"date-parts":[[2017,6,27]],"date-time":"2017-06-27T00:30:31Z","timestamp":1498523431000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":18,"title":["Targeting the Homoserine Dehydrogenase of Paracoccidioides Species for Treatment of Systemic Fungal Infections"],"prefix":"10.1128","volume":"61","author":[{"given":"Mariane C.","family":"Bagatin","sequence":"first","affiliation":[{"name":"Department of Chemistry, State University of Maring\u00e1, Maring\u00e1, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arethusa L.","family":"Pimentel","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, State University of Maring\u00e1, Maring\u00e1, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00e9bora C.","family":"Biavatti","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, State University of Maring\u00e1, Maring\u00e1, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernani A.","family":"Basso","sequence":"additional","affiliation":[{"name":"Department of Chemistry, State University of Maring\u00e1, Maring\u00e1, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika S.","family":"Kioshima","sequence":"additional","affiliation":[{"name":"Department of Clinical Analysis and Biomedicine, State University of Maring\u00e1, Maring\u00e1, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavio A. V.","family":"Seixas","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, State University of Maring\u00e1, Maring\u00e1, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisele de F.","family":"Gauze","sequence":"additional","affiliation":[{"name":"Department of Chemistry, State University of Maring\u00e1, Maring\u00e1, PR, 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