دورية أكاديمية
أعرض في EDS

Two New 1,3,4-Oxadiazoles With Effective Antifungal Activity Against Candida albicans .

التفاصيل البيبلوغرافية
العنوان: Two New 1,3,4-Oxadiazoles With Effective Antifungal Activity Against Candida albicans .
المؤلفون: Capoci IRG; Department of Clinical Analysis and Biomedicine, The State University of Maringá, Maringá, Brazil., Sakita KM; Department of Clinical Analysis and Biomedicine, The State University of Maringá, Maringá, Brazil., Faria DR; Department of Clinical Analysis and Biomedicine, The State University of Maringá, Maringá, Brazil., Rodrigues-Vendramini FAV; Department of Clinical Analysis and Biomedicine, The State University of Maringá, Maringá, Brazil., Arita GS; Department of Clinical Analysis and Biomedicine, The State University of Maringá, Maringá, Brazil., de Oliveira AG; Laboratory of Electron Microscopy and Microanalysis, State University of Londrina, Londrina, Brazil., Felipe MS; Department of Cellular Biology, The University of Brasília, Brasília, Brazil., Maigret B; LORIA, University of Lorraine, Nancy, France., Bonfim-Mendonça PS; Department of Clinical Analysis and Biomedicine, The State University of Maringá, Maringá, Brazil., Kioshima ES; Department of Clinical Analysis and Biomedicine, The State University of Maringá, Maringá, Brazil., Svidzinski TIE; Department of Clinical Analysis and Biomedicine, The State University of Maringá, Maringá, Brazil.
المصدر: Frontiers in microbiology [Front Microbiol] 2019 Sep 12; Vol. 10, pp. 2130. Date of Electronic Publication: 2019 Sep 12 (Print Publication: 2019).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Frontiers Research Foundation Country of Publication: Switzerland NLM ID: 101548977 Publication Model: eCollection Cited Medium: Print ISSN: 1664-302X (Print) Linking ISSN: 1664302X NLM ISO Abbreviation: Front Microbiol Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Lausanne : Frontiers Research Foundation
مستخلص: Candida infections have become a serious public health problem with high mortality rates, especially in immunocompromised patients, since Candida albicans is the major opportunistic pathogen responsible for systemic or invasive candidiasis. Commercially available antifungal agents are restricted and fungal resistance to such drugs has increased; therefore, the development of a more specific antifungal agent is necessary. Using assays for antifungal activity, here we report that two new compounds of 1,3,4-oxadiazoles class (LMM5 and LMM11), which were discovered by in silico methodologies as possible thioredoxin reductase inhibitors, were effective against C. albicans . Both compounds had in vitro antifungal activity with MIC 32 μg/ml. Cytotoxicity in vitro demonstrated that LMM5 and LMM11 were non-toxic in the cell lines evaluated. The kinetic of the time-kill curve suggested a fungistatic profile and showed an inhibitory effect of LMM5 and LMM11 in 12 h that remained for 24 and 36 h, which is better than fluconazole. In the murine systemic candidiasis model by C. albicans , the two compounds significantly reduced the renal and spleen fungal burden. According to the SEM and TEM images, we hypothesize that the mechanism of action of LMM5 and LMM11 is directly related to the inhibition of the enzyme thioredoxin reductase and internally affect the fungal cell. In view of all in vitro and in vivo results, LMM5 and LMM11 are effective therapeutic candidates for the development of new antifungal drugs addressing the treatment of human infections caused by C. albicans .
(Copyright © 2019 Capoci, Sakita, Faria, Rodrigues-Vendramini, Arita, de Oliveira, Felipe, Maigret, Bonfim-Mendonça, Kioshima and Svidzinski.)
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فهرسة مساهمة: Keywords: Candida albicans; antifungal activity; in vitro; in vivo; thioredoxin reductase
تواريخ الأحداث: Date Created: 20191002 Latest Revision: 20201001
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC6751290
DOI: 10.3389/fmicb.2019.02130
PMID: 31572335
قاعدة البيانات: MEDLINE
الوصف
تدمد:1664-302X
DOI:10.3389/fmicb.2019.02130