{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T13:34:02Z","timestamp":1762176842803},"reference-count":48,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2015,12,1]],"date-time":"2015-12-01T00:00:00Z","timestamp":1448928000000},"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":[[2015,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Paracoccidioidomycosis (PCM), caused by\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, is the main cause of death due to systemic mycoses in Brazil and other Latin American countries. Therapeutic options for PCM and other systemic mycoses are limited and time-consuming, and there are high rates of noncompliance, relapses, toxic side effects, and sequelae. Previous work has shown that the cyclopalladated 7a compound is effective in treating several kinds of cancer and parasitic Chagas disease without significant toxicity in animals. Here we show that cyclopalladated 7a inhibited the\n            <jats:italic>in vitro<\/jats:italic>\n            growth 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            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">lutzii<\/jats:named-content>\n            Pb01 and\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. brasiliensis<\/jats:named-content>\n            isolates Pb18 (highly virulent), Pb2, Pb3, and Pb4 (less virulent) in a dose-response manner. Pb18 was the most resistant. Opportunistic\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Candida albicans<\/jats:named-content>\n            and\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Cryptococcus neoformans<\/jats:named-content>\n            were also sensitive. BALB\/c mice showed significantly lighter lung fungal burdens when treated twice a day for 20 days with a low cyclopalladated 7a dose of 30 \u03bcg\/ml\/day for 30 days after intratracheal infection with Pb18. Electron microscopy images suggested that apoptosis- and autophagy-like mechanisms are involved in the fungal killing mechanism of cyclopalladated 7a. Pb18 yeast cells incubated with the 7a compound showed remarkable chromatin condensation, DNA degradation, superoxide anion production, and increased metacaspase activity suggestive of apoptosis. Autophagy-related killing mechanisms were suggested by increased autophagic vacuole numbers and acidification, as indicated by an increase in LysoTracker and monodansylcadaverine (MDC) staining in cyclopalladated 7a-treated Pb18 yeast cells. Considering that cyclopalladated 7a is highly tolerated\n            <jats:italic>in vivo<\/jats:italic>\n            and affects yeast fungal growth through general apoptosis- and autophagy-like mechanisms, it is a novel promising drug for the treatment of PCM and other mycoses.\n          <\/jats:p>","DOI":"10.1128\/aac.00512-15","type":"journal-article","created":{"date-parts":[[2015,9,9]],"date-time":"2015-09-09T02:21:18Z","timestamp":1441765278000},"page":"7214-7223","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":7,"title":["Cyclopalladated Compound 7a Induces Apoptosis- and Autophagy-Like Mechanisms in Paracoccidioides and Is a Candidate for Paracoccidioidomycosis Treatment"],"prefix":"10.1128","volume":"59","author":[{"given":"Denise C.","family":"Arruda","sequence":"first","affiliation":[{"name":"Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina-Universidade Federal de S\u00e3o Paulo, EPM-UNIFESP, S\u00e3o Paulo, SP, Brazil"},{"name":"N\u00facleo Integrado de Biotecnologia, Universidade de Mogi das Cruzes, UMC, Mogi das Cruzes, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alisson L.","family":"Matsuo","sequence":"additional","affiliation":[{"name":"Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina-Universidade Federal de S\u00e3o Paulo, EPM-UNIFESP, S\u00e3o Paulo, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luiz S.","family":"Silva","sequence":"additional","affiliation":[{"name":"Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina-Universidade Federal de S\u00e3o Paulo, EPM-UNIFESP, S\u00e3o Paulo, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando","family":"Real","sequence":"additional","affiliation":[{"name":"Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina-Universidade Federal de S\u00e3o Paulo, EPM-UNIFESP, S\u00e3o Paulo, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"Natanael P.","family":"Leit\u00e3o","sequence":"additional","affiliation":[{"name":"Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina-Universidade Federal de S\u00e3o Paulo, EPM-UNIFESP, S\u00e3o Paulo, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jhon H. S.","family":"Pires","sequence":"additional","affiliation":[{"name":"Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina-Universidade Federal de S\u00e3o Paulo, EPM-UNIFESP, S\u00e3o Paulo, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio Carlos F.","family":"Caires","sequence":"additional","affiliation":[{"name":"Centro Interdisciplinar de Investiga\u00e7\u00e3o Bioqu\u00edmica, Universidade de Mogi das Cruzes, UMC, Mogi das Cruzes, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel M.","family":"Garcia","sequence":"additional","affiliation":[{"name":"Centro Interdisciplinar de Investiga\u00e7\u00e3o Bioqu\u00edmica, Universidade de Mogi das Cruzes, UMC, Mogi das Cruzes, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernanda F. 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