Antifungal activity of two oxadiazole compounds for the paracoccidioidomycosis treatment

Autor: Rodrigues-Vendramini, Franciele Abigail Vilugron, Faria, Daniella Renata, Arita, Glaucia Sayuri, Capoci, Isis Regina Grenier, Sakita, Karina Mayumi, Caparroz-Assef, Silvana Martins, Becker, Tania Cristina Alexandrino, de Souza Bonfim-Mendonça, Patrícia, Felipe, Maria Sueli, Svidzinski, Terezinha Inez Estivalet, Maigret, Bernard, Kioshima, Erika Seki, Small, Pamela
Přispěvatelé: Universidade Estadual de Maringá [Maringá] (UEM), University of Brasilia [Brazil] (UnB), Computational Algorithms for Protein Structures and Interactions (CAPSID), Inria Nancy - Grand Est, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Department of Complex Systems, Artificial Intelligence & Robotics (LORIA - AIS), Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Department of Cellular Biology [Brasilia], Universidade de Brasilia [Brasília] (UnB), The University of Tennessee [Knoxville]
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Male
0301 basic medicine
Fungal Structure
Antifungal Agents
RC955-962
Colony Count
Microbial
Pharmacology
Pathology and Laboratory Medicine
Toxicology
Paracoccidioides
chemistry.chemical_compound
Fluorescence Microscopy
0302 clinical medicine
Arctic medicine. Tropical medicine
Medicine and Health Sciences
Immune Response
Lung
Fungicides
Microscopy
Mice
Inbred BALB C
Oxadiazoles
Antimicrobials
Histocytochemistry
Paracoccidioidomycosis
Histopathological analysis
Fungal Diseases
Drugs
Light Microscopy
Eukaryota
Agriculture
Drug Synergism
3. Good health
Fungicide
Treatment Outcome
Infectious Diseases
Toxicity
Public aspects of medicine
RA1-1270
Agrochemicals
Research Article
Neglected Tropical Diseases
Antifungal
medicine.drug_class
Immunology
030231 tropical medicine
Oxadiazole
Mycology
Microbial Sensitivity Tests
Research and Analysis Methods
Microbiology
03 medical and health sciences
Signs and Symptoms
Pharmacotherapy
Diagnostic Medicine
Microbial Control
Amphotericin B
medicine
Animals
Inflammation
Antifungals
Microbial Viability
Organisms
Fungi
Public Health
Environmental and Occupational Health
Biology and Life Sciences
Tropical Diseases
medicine.disease
Disease Models
Animal
030104 developmental biology
chemistry
[INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM]
Zdroj: PLoS Neglected Tropical Diseases
PLoS Neglected Tropical Diseases, Public Library of Science, 2019, 13 (6), pp.e0007441. ⟨10.1371/journal.pntd.0007441⟩
PLoS Neglected Tropical Diseases, 2019, 13 (6), pp.e0007441. ⟨10.1371/journal.pntd.0007441⟩
PLoS Neglected Tropical Diseases, Vol 13, Iss 6, p e0007441 (2019)
ISSN: 1935-2727
1935-2735
DOI: 10.1371/journal.pntd.0007441⟩
Popis: Paracoccidioidomycosis (PCM) is a neglected disease present in Latin America with difficulty in treatment and occurrence of serious sequelae. Thus, the development of alternative therapies is imperative. In the current work, two oxadiazole compounds (LMM5 and LMM11) presented fungicidal activity against Paracoccidioides spp. The minimum inhibitory and fungicidal concentration values ranged from 1 to 32 μg/mL, and a synergic effect was observed for both compounds when combined with Amphotericin B. LMM5 and LMM11 were able to reduce CFU counts (≥2 log10) on the 5th and 7th days of time-kill curve, respectively. The fungicide effect was confirmed by fluorescence microscopy (FUN-1/FUN-2). The hippocratic screening and biochemical analysis were performed in Balb/c male mice that received a high dose of each compound, and the compounds showed no in vivo toxicity. The treatment of experimental PCM with the new oxadiazoles led to significant reduction in CFU (≥1 log10). Histopathological analysis of the groups treated exhibited control of inflammation, as well as preserved lung areas. These findings suggest that LMM5 and LMM11 are promising hits structures, opening the door for implementing new PCM therapies.
Author summary Paracoccidioidomycosis (PCM) is a granulomatous fungal infection with clinically severe forms and serious pulmonary sequelae. The current limited arsenal and prolonged treatment regimen demonstrate the need for new antifungals. This study reveals two fungicidal oxadiazole compounds for PCM treatment. The in vitro assay showed the antifungal activity and the synergic effect with Amphotericin B. The high doses administration in mice showed absence of toxicity, which allowed to demonstrate the in vivo antifungal activity.
Databáze: OpenAIRE
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