Fungicidal Activity of a Safe 1,3,4-Oxadiazole Derivative against Candida albicans

Pathogens

TaniaCristina Alexandrino Becker¹  GlauciaSayuri Arita²  TerezinhaInez Estivalet Svidzinski²  RaquelCabral Melo²  FrancieleAbigail Vilugron Rodrigues-Vendramini²  Patríciade Souza Bonfim-Mendonça²  DaniellaRenata Faria²  IsisRegina Grenier Capoci²  ErikaSeki Kioshima²  KarinaMayumi Sakita²  MariaSueli Soares Felipe³ 

[1] Laboratory of General Pathology, Department of Basic Health Sciences, State University of Maringá, Maringá (UEM), Maringá, Paraná 87020-900, Brazil;Laboratory of Medical Mycology, Department of Clinical Analysis and Biomedicine, State University of Maringá (UEM), Maringá, Paraná 87020-900, Brazil;Program of Genomic Sciences and Biotechnology, Catholic University of Brasilia, Brasília 70790-160, Brazil;

关键词: Candida albicans;    candidiasis;    1,3,4-oxadiazole;    drug discovery;    antifungal agents;    drug resistance;   

DOI  :  10.3390/pathogens10030314

来源: DOAJ

【 摘 要 】

Candida albicans is the most common species isolated from nosocomial bloodstream infections. Due to limited therapeutic arsenal and increase of drug resistance, there is an urgent need for new antifungals. Therefore, the antifungal activity against C. albicans and in vivo toxicity of a 1,3,4-oxadiazole compound (LMM6) was evaluated. This compound was selected by in silico approach based on chemical similarity. LMM6 was highly effective against several clinical C. albicans isolates, with minimum inhibitory concentration values ranging from 8 to 32 µg/mL. This compound also showed synergic effect with amphotericin B and caspofungin. In addition, quantitative assay showed that LMM6 exhibited a fungicidal profile and a promising anti-biofilm activity, pointing to its therapeutic potential. The evaluation of acute toxicity indicated that LMM6 is safe for preclinical trials. No mortality and no alterations in the investigated parameters were observed. In addition, no substantial alteration was found in Hippocratic screening, biochemical or hematological analyzes. LMM6 (5 mg/kg twice a day) was able to reduce both spleen and kidneys fungal burden and further, promoted the suppresses of inflammatory cytokines, resulting in infection control. These preclinical findings support future application of LMM6 as potential antifungal in the treatment of invasive candidiasis.

【 授权许可】

Unknown