PMID- 30148835
OWN - NLM
STAT- MEDLINE
DCOM- 20190208
LR  - 20190215
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 13
IP  - 8
DP  - 2018
TI  - Chemoproteomic identification of molecular targets of antifungal prototypes, 
      thiosemicarbazide and a camphene derivative of thiosemicarbazide, in 
      Paracoccidioides brasiliensis.
PG  - e0201948
LID - 10.1371/journal.pone.0201948 [doi]
LID - e0201948
AB  - Paracoccidioidomycosis (PCM) is a neglected human systemic disease caused by 
      species of the genus Paracoccidioides. The disease attacks the host's lungs and 
      may disseminate to many other organs. Treatment involves amphotericin B, 
      sulfadiazine, trimethoprim-sulfamethoxazole, itraconazole, ketoconazole, or 
      fluconazole. The treatment duration is usually long, from 6 months to 2 years, 
      and many adverse effects may occur in relation to the treatment; co-morbidities 
      and poor treatment adherence have been noted. Therefore, the discovery of more 
      effective and less toxic drugs is needed. Thiosemicarbazide (TSC) and a camphene 
      derivative of thiosemicarbazide (TSC-C) were able to inhibit P. brasiliensis 
      growth at a low dosage and were not toxic to fibroblast cells. In order to 
      investigate the mode of action of those compounds, we used a chemoproteomic 
      approach to determine which fungal proteins were bound to each of these 
      compounds. The compounds were able to inhibit the activities of the enzyme 
      formamidase and interfered in P. brasiliensis dimorphism. In comparison with the 
      transcriptomic and proteomic data previously obtained by our group, we determined 
      that TSC and TSC-C were multitarget compounds that exerted effects on the 
      electron-transport chain and cell cycle regulation, increased ROS formation, 
      inhibited proteasomes and peptidases, modulated glycolysis, lipid, protein and 
      carbohydrate metabolisms, and caused suppressed the mycelium to yeast transition.
FAU - Borba, Joyce Villa Verde Bastos
AU  - Borba JVVB
AD  - Laboratorio de Biologia Molecular, Instituto de Ciencias Biologicas, Universidade 
      Federal de Goias, Goiania, Goias, Brazil.
FAU - Tauhata, Sinji Borges Ferreira
AU  - Tauhata SBF
AD  - Laboratorio de Biologia Molecular, Instituto de Ciencias Biologicas, Universidade 
      Federal de Goias, Goiania, Goias, Brazil.
FAU - Oliveira, Cecilia Maria Alves de
AU  - Oliveira CMA
AD  - Laboratorio de Produtos Naturais, Instituto de Quimica, Universidade Federal de 
      Goias, Goiania, Goias, Brazil.
FAU - Ferreira Marques, Monique
AU  - Ferreira Marques M
AD  - Laboratorio de Produtos Naturais, Instituto de Quimica, Universidade Federal de 
      Goias, Goiania, Goias, Brazil.
FAU - Bailao, Alexandre Melo
AU  - Bailao AM
AD  - Laboratorio de Biologia Molecular, Instituto de Ciencias Biologicas, Universidade 
      Federal de Goias, Goiania, Goias, Brazil.
FAU - Soares, Celia Maria de Almeida
AU  - Soares CMA
AD  - Laboratorio de Biologia Molecular, Instituto de Ciencias Biologicas, Universidade 
      Federal de Goias, Goiania, Goias, Brazil.
FAU - Pereira, Maristela
AU  - Pereira M
AUID- ORCID: 0000-0002-5482-8036
AD  - Laboratorio de Biologia Molecular, Instituto de Ciencias Biologicas, Universidade 
      Federal de Goias, Goiania, Goias, Brazil.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180827
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antifungal Agents)
RN  - 0 (Fungal Proteins)
RN  - 0 (Semicarbazides)
RN  - 6056O8W6ET (thiosemicarbazide)
RN  - EC 3.5.- (Amidohydrolases)
RN  - EC 3.5.1.49 (formamidase)
SB  - IM
MH  - Amidohydrolases/metabolism
MH  - Animals
MH  - Antifungal Agents/*chemistry/isolation & purification/*pharmacology
MH  - BALB 3T3 Cells
MH  - Cell Survival/drug effects
MH  - Drug Discovery
MH  - Enzyme Activation/drug effects
MH  - Fungal Proteins/antagonists & inhibitors/*metabolism
MH  - Humans
MH  - Mice
MH  - Microbial Sensitivity Tests
MH  - Paracoccidioides/*drug effects/*metabolism
MH  - Protein Binding
MH  - *Proteomics/methods
MH  - Semicarbazides/*chemistry/isolation & purification/*pharmacology
PMC - PMC6110461
COIS- The authors have declared that no competing interests exist.
EDAT- 2018/08/28 06:00
MHDA- 2019/02/09 06:00
PMCR- 2018/08/27
CRDT- 2018/08/28 06:00
PHST- 2018/02/20 00:00 [received]
PHST- 2018/07/25 00:00 [accepted]
PHST- 2018/08/28 06:00 [entrez]
PHST- 2018/08/28 06:00 [pubmed]
PHST- 2019/02/09 06:00 [medline]
PHST- 2018/08/27 00:00 [pmc-release]
AID - PONE-D-18-05592 [pii]
AID - 10.1371/journal.pone.0201948 [doi]
PST - epublish
SO  - PLoS One. 2018 Aug 27;13(8):e0201948. doi: 10.1371/journal.pone.0201948. 
      eCollection 2018.