PMID- 31163021
OWN - NLM
STAT- MEDLINE
DCOM- 20191127
LR  - 20200309
IS  - 1935-2735 (Electronic)
IS  - 1935-2727 (Print)
IS  - 1935-2727 (Linking)
VI  - 13
IP  - 6
DP  - 2019 Jun
TI  - Antifungal activity of two oxadiazole compounds for the paracoccidioidomycosis 
      treatment.
PG  - e0007441
LID - 10.1371/journal.pntd.0007441 [doi]
LID - e0007441
AB  - 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 mug/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.
FAU - Rodrigues-Vendramini, Franciele Abigail Vilugron
AU  - Rodrigues-Vendramini FAV
AD  - Department of Clinical and Biomedical Analysis, State University of Maringa, 
      Maringa, Brazil.
FAU - Faria, Daniella Renata
AU  - Faria DR
AD  - Department of Clinical and Biomedical Analysis, State University of Maringa, 
      Maringa, Brazil.
FAU - Arita, Glaucia Sayuri
AU  - Arita GS
AD  - Department of Clinical and Biomedical Analysis, State University of Maringa, 
      Maringa, Brazil.
FAU - Capoci, Isis Regina Grenier
AU  - Capoci IRG
AD  - Department of Clinical and Biomedical Analysis, State University of Maringa, 
      Maringa, Brazil.
FAU - Sakita, Karina Mayumi
AU  - Sakita KM
AD  - Department of Clinical and Biomedical Analysis, State University of Maringa, 
      Maringa, Brazil.
FAU - Caparroz-Assef, Silvana Martins
AU  - Caparroz-Assef SM
AD  - Department of Pharmacology and Therapeutics, State University of Maringa, 
      Maringa, Brazil.
FAU - Becker, Tania Cristina Alexandrino
AU  - Becker TCA
AD  - Department of Basic Health Sciences, State University of Maringa, Maringa, 
      Brazil.
FAU - de Souza Bonfim-Mendonca, Patricia
AU  - de Souza Bonfim-Mendonca P
AD  - Department of Clinical and Biomedical Analysis, State University of Maringa, 
      Maringa, Brazil.
FAU - Felipe, Maria Sueli
AU  - Felipe MS
AD  - Department of Cell Biology, Institute of Biological Sciences, University of 
      Brasilia, Brazil.
FAU - Svidzinski, Terezinha Inez Estivalet
AU  - Svidzinski TIE
AD  - Department of Clinical and Biomedical Analysis, State University of Maringa, 
      Maringa, Brazil.
FAU - Maigret, Bernard
AU  - Maigret B
AD  - LORIA, Lorraine University, Nancy, France.
FAU - Kioshima, Erika Seki
AU  - Kioshima ES
AUID- ORCID: 0000-0003-3290-8577
AD  - Department of Clinical and Biomedical Analysis, State University of Maringa, 
      Maringa, Brazil.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190604
PL  - United States
TA  - PLoS Negl Trop Dis
JT  - PLoS neglected tropical diseases
JID - 101291488
RN  - 0 (Antifungal Agents)
RN  - 0 (Oxadiazoles)
RN  - 7XU7A7DROE (Amphotericin B)
SB  - IM
MH  - Amphotericin B/pharmacology
MH  - Animals
MH  - Antifungal Agents/administration & dosage/*pharmacology
MH  - Colony Count, Microbial
MH  - Disease Models, Animal
MH  - Drug Synergism
MH  - Histocytochemistry
MH  - Lung/microbiology/pathology
MH  - Male
MH  - Mice, Inbred BALB C
MH  - Microbial Sensitivity Tests
MH  - Microbial Viability/drug effects
MH  - Oxadiazoles/administration & dosage/*pharmacology
MH  - Paracoccidioides/*drug effects
MH  - Paracoccidioidomycosis/drug therapy/microbiology/pathology
MH  - Treatment Outcome
PMC - PMC6548352
COIS- The authors have declared that no competing interests exist.
EDAT- 2019/06/05 06:00
MHDA- 2019/11/28 06:00
PMCR- 2019/06/04
CRDT- 2019/06/05 06:00
PHST- 2018/12/13 00:00 [received]
PHST- 2019/05/06 00:00 [accepted]
PHST- 2019/06/05 06:00 [entrez]
PHST- 2019/06/05 06:00 [pubmed]
PHST- 2019/11/28 06:00 [medline]
PHST- 2019/06/04 00:00 [pmc-release]
AID - PNTD-D-18-01983 [pii]
AID - 10.1371/journal.pntd.0007441 [doi]
PST - epublish
SO  - PLoS Negl Trop Dis. 2019 Jun 4;13(6):e0007441. doi: 10.1371/journal.pntd.0007441. 
      eCollection 2019 Jun.