دورية أكاديمية
Thiosemicarbazone of lapachol acts on cell membrane in Paracoccidioides brasiliensis.
| العنوان: | Thiosemicarbazone of lapachol acts on cell membrane in Paracoccidioides brasiliensis. |
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| المؤلفون: | de Sá NP; Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Cisalpino PS; Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Bertollo CM; Laboratory of Chemistry of Natural Products, René Rachou Research Center, FIOCRUZ, Belo Horizonte, MG, Brazil., Santos PC; Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Rosa CA; Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., de Souza DDG; Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Barbeira PJS; Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Alves TMA; Laboratory of Chemistry of Natural Products, René Rachou Research Center, FIOCRUZ, Belo Horizonte, MG, Brazil., Zani CL; Laboratory of Chemistry of Natural Products, René Rachou Research Center, FIOCRUZ, Belo Horizonte, MG, Brazil., Johann S; Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil. |
| المصدر: | Medical mycology [Med Mycol] 2019 Apr 01; Vol. 57 (3), pp. 332-339. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: England NLM ID: 9815835 Publication Model: Print Cited Medium: Internet ISSN: 1460-2709 (Electronic) Linking ISSN: 13693786 NLM ISO Abbreviation: Med Mycol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2014- : Oxford : Oxford University Press Original Publication: Oxford : Blackwell Science, c1998- |
| مواضيع طبية MeSH: | Antifungal Agents/*pharmacology , Cell Membrane/*drug effects , Naphthoquinones/*pharmacology , Paracoccidioides/*drug effects , Thiosemicarbazones/*pharmacology, Animals ; Ergosterol/biosynthesis ; Macrophages/drug effects ; Male ; Mice ; Mice, Inbred BALB C ; Microbial Sensitivity Tests ; Paracoccidioidomycosis/drug therapy ; Paracoccidioidomycosis/microbiology ; Phagocytosis/drug effects |
| مستخلص: | Paracoccidioidomycosis (PCM) is the most prevalent systemic mycosis in Latin American countries. Amphotericin B, sulfonamides, and azoles may be used in the treatment of PCM. However, the high toxicity, prolonged course of treatment, and significant frequency of disease relapse compromise their use. Therefore, there is a need to seek new therapeutic options. We conducted tests with thiosemicarbazone of lapachol (TSC-lap) to determine the antifungal activity and phenotypic effects against several isolates of Paracoccidioides spp. In addition, we evaluated the toxicity against murine macrophages and the ability to enhance phagocytosis. Further, we verified that TSC-lap was active against yeasts but did not show any interaction with the drugs tested. The TSC-lap showed no toxicity at the concentration of 40 μg/ml in macrophages, and at 15.6 μg/ml it could increase the phagocytic index. We observed that this compound induced in vitro ultrastructural changes manifested as withered and broken cells beyond a disorganized cytoplasm with accumulation of granules. We did not observe indications of activity in the cell wall, although membrane damages were noted. We observed alterations in the membrane permeability, culminating in a significant increase in K+ efflux and a gradual loss of the cellular content with increase in the concentration of TSC-lap. In addition, we showed a significant reduction of ergosterol amount in the Pb18 membrane. These data reinforce the possible mechanism of action of this compound to be closely associated with ergosterol biosynthesis and reaffirms the antifungal potential of TSC-lap against Paracoccidioides spp. (© The Author(s) 2018. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.) |
| فهرسة مساهمة: | Keywords: Paracoccidioides; Antifungal; ergosterol; thiosemicarbazone of lapachol |
| المشرفين على المادة: | 0 (Antifungal Agents) 0 (Naphthoquinones) 0 (Thiosemicarbazones) B221938VB6 (lapachol) Z30RAY509F (Ergosterol) |
| تواريخ الأحداث: | Date Created: 20180627 Date Completed: 20190404 Latest Revision: 20190404 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1093/mmy/myy045 |
| PMID: | 29945180 |
| قاعدة البيانات: | MEDLINE |
PDF full text from Publisher | تدمد: | 1460-2709 |
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| DOI: | 10.1093/mmy/myy045 |