A Highly Active Triterpene Derivative Capable of Biofilm Damage to Control Cryptococcus spp.

Autor(es)

Krummenauer, Maria E. ^[1] ; Lopes, William ^[1] ; Garcia, Ane W. A. ^[1] ; Schrank, Augusto ^[1] ; Gnoatto, Simone C. B. ^[2] ; Kawano, Daniel F. ^[3] ; Vainstein, Marilene H. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Rio Grande do Sul, Ctr Biotecnol, PPGBCM, BR-91501970 Porto Alegre, RS - Brazil

^[2] Univ Fed Rio Grande do Sul, Fac Farm, BR-90610000 Porto Alegre, RS - Brazil

^[3] Univ Estadual Campinas, Fac Ciencias Farmaceut, BR-13083871 Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BIOMOLECULES; v. 9, n. 12 DEC 2019.
• Citações Web of Science: 0

Resumo

Cryptococcus neoformans is an encapsulated yeast responsible for more than 180,000 deaths per year. The standard therapeutic approach against cryptococcosis is a combination of amphotericin B with flucytosine. In countries where cryptococcosis is most prevalent, 5-fluorocytosine is rarely available, and amphotericin B requires intravenous administration. C. neoformans biofilm formation is related to increased drug resistance, which is an important outcome for hospitalized patients. Here, we describe new molecules with anti-cryptococcal activity. A collection of 66 semisynthetic derivatives of ursolic acid and betulinic acid was tested against mature biofilms of C. neoformans at 25 mu M. Out of these, eight derivatives including terpenes, benzazoles, flavonoids, and quinolines were able to cause damage and eradicate mature biofilms. Four terpene compounds demonstrated significative growth inhibition of C. neoformans. Our study identified a pentacyclic triterpenoid derived from betulinic acid (LAFIS13) as a potential drug for anti-cryptococcal treatment. This compound appears to be highly active with low toxicity at minimal inhibitory concentration and capable of biofilm eradication. (AU)

• Processo FAPESP: 18/08585-1 - Planejamento e síntese de novos fosfolipídios capazes de induzir seletivamente a apoptose de células tumorais pela atuação em "lipid rafts"
• Beneficiário: Daniel Fábio Kawano
• Modalidade de apoio: Auxílio à Pesquisa - Regular