{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T03:29:32Z","timestamp":1777519772344,"version":"3.51.4"},"reference-count":40,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2015,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Paracoccidioides<\/jats:named-content>\n            is the agent of paracoccidioidomycosis. Malate synthase plays a crucial role in the pathogenicity and virulence of various fungi, such as those that are human pathogens. Thus, an inhibitor of this enzyme may be used as a powerful antifungal without side effects in patients once these enzymes are absent in humans. Here, we searched for compounds with inhibitory capacity against the malate synthase of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Paracoccidioides<\/jats:named-content>\n            species (\n            <jats:italic>Pb<\/jats:italic>\n            MLS). The three-dimensional (3D) structure of\n            <jats:italic>Pb<\/jats:italic>\n            MLS was determined using the I-TASSER server. Compounds were selected from the ZINC database. Based on the mechanism underlying the interaction of the compounds with\n            <jats:italic>Pb<\/jats:italic>\n            MLS, it was possible to identify \u03b2-carboline moiety as a standard key structure. The compounds with \u03b2-carboline moiety that are available in our laboratories were investigated. A total of nine alkaloid compounds were selected. The primary mechanisms of interaction of the alkaloid compounds in the binding pocket of\n            <jats:italic>Pb<\/jats:italic>\n            MLS were identified and compared with the mechanism of interaction of acetyl coenzyme A (acetyl-CoA). We discovered that the amphipathic nature of the compounds, concomitant with the presence of \u03b2-carboline moiety, was crucial for their stability in the binding pocket of\n            <jats:italic>Pb<\/jats:italic>\n            MLS. In addition, the importance of a critical balance of the polar and nonpolar contacts of the compounds in this region was observed. Four \u03b2-carboline alkaloid compounds showed the ability to inhibit recombinant\n            <jats:italic>Pb<\/jats:italic>\n            MLS (\n            <jats:italic>Pb<\/jats:italic>\n            MLSr) activity,\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Paracoccidioides<\/jats:named-content>\n            species growth, and adhesion of the fungus and\n            <jats:italic>Pb<\/jats:italic>\n            MLSr to the extracellular matrix components. The cytotoxicity of the alkaloids was also evaluated.\n          <\/jats:p>","DOI":"10.1128\/aac.04711-14","type":"journal-article","created":{"date-parts":[[2015,6,30]],"date-time":"2015-06-30T02:44:58Z","timestamp":1435632298000},"page":"5581-5594","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":26,"title":["Alkaloids as Inhibitors of Malate Synthase from Paracoccidioides spp.: Receptor-Ligand Interaction-Based Virtual Screening and Molecular Docking Studies, Antifungal Activity, and the Adhesion Process"],"prefix":"10.1128","volume":"59","author":[{"given":"Fausto Guimaraes","family":"Costa","sequence":"first","affiliation":[{"name":"N\u00facleo Colaborativo de BioSistemas, Regional Jata\u00ed, Universidade Federal de Goi\u00e1s, Jata\u00ed, Goi\u00e1s, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benedito Rodrigues da Silva","family":"Neto","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Molecular, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Goi\u00e1s, Goi\u00e2nia, Goi\u00e1s, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo Lemes","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"N\u00facleo Colaborativo de BioSistemas, Regional Jata\u00ed, Universidade Federal de Goi\u00e1s, Jata\u00ed, Goi\u00e1s, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roosevelt Alves","family":"da Silva","sequence":"additional","affiliation":[{"name":"N\u00facleo Colaborativo de BioSistemas, Regional Jata\u00ed, Universidade Federal de Goi\u00e1s, Jata\u00ed, Goi\u00e1s, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cec\u00edlia Maria Alves","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Produtos Naturais, Instituto de Qu\u00edmica, Universidade Federal de Goi\u00e1s, Goi\u00e2nia, Goi\u00e1s, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luc\u00edlia","family":"Kato","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Produtos Naturais, Instituto de Qu\u00edmica, Universidade Federal de Goi\u00e1s, Goi\u00e2nia, Goi\u00e1s, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla dos Santos","family":"Freitas","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Produtos Naturais, Instituto de Qu\u00edmica, Universidade Federal de Goi\u00e1s, Goi\u00e2nia, Goi\u00e1s, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Jos\u00e9 Soares Mendes","family":"Giannini","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Micologia Cl\u00ednica, Universidade Estadual J\u00falio de Mesquita Melo, Araraquara, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julhiany de F\u00e1tima","family":"da Silva","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Micologia Cl\u00ednica, Universidade Estadual J\u00falio de Mesquita Melo, Araraquara, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C\u00e9lia Maria de Almeida","family":"Soares","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Molecular, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Goi\u00e1s, Goi\u00e2nia, Goi\u00e1s, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maristela","family":"Pereira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Molecular, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Goi\u00e1s, Goi\u00e2nia, Goi\u00e1s, 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