PMID- 30150478
OWN - NLM
STAT- MEDLINE
DCOM- 20191010
LR  - 20200511
IS  - 1098-6596 (Electronic)
IS  - 0066-4804 (Print)
IS  - 0066-4804 (Linking)
VI  - 62
IP  - 11
DP  - 2018 Nov
TI  - Argentilactone Molecular Targets in Paracoccidioides brasiliensis Identified by 
      Chemoproteomics.
LID - 10.1128/AAC.00737-18 [doi]
LID - e00737-18
AB  - Paracoccidioidomycosis (PCM) is the cause of many deaths from systemic mycoses. 
      The etiological agents of PCM belong to the Paracoccidioides genus, which is 
      restricted to Latin America. The infection is acquired through the inhalation of 
      conidia that primarily lodge in the lungs and may disseminate to other organs and 
      tissues. The treatment for PCM is commonly performed via the administration of 
      antifungals such as amphotericin B, co-trimoxazole, and itraconazole. The 
      antifungal toxicity and side effects, in addition to their long treatment times, 
      have stimulated research for new bioactive compounds. Argentilactone is a 
      compound that was isolated from the Brazilian savanna plant Hyptis ovalifolia, 
      and it has been suggested to be a potent antifungal, inhibiting the dimorphism of 
      P. brasiliensis and the enzymatic activity of isocitrate lyase, a key enzyme of 
      the glyoxylate cycle. This work was developed due to the importance of 
      elucidating the putative mode of action of argentilactone. The chemoproteomics 
      approach via affinity chromatography was the methodology used to explore the 
      interactions between P. brasiliensis proteins and argentilactone. A total of 109 
      proteins were identified and classified functionally. The most representative 
      functional categories were related to amino acid metabolism, energy, and 
      detoxification. Argentilactone inhibited the enzymatic activity of malate 
      dehydrogenase, citrate synthase, and pyruvate dehydrogenase. Furthermore, 
      argentilactone induces the production of reactive oxygen species and inhibits the 
      biosynthesis of cell wall polymers.
CI  - Copyright (c) 2018 American Society for Microbiology.
FAU - Silva, Livia do Carmo
AU  - Silva LDC
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 - Baeza, Lilian Cristiane
AU  - Baeza LC
AD  - Laboratorio de Biologia Molecular, Instituto de Ciencias Biologicas, Universidade 
      Federal de Goias, Goiania, Goias, Brazil.
AD  - Centro de Ciencias Medicas e Farmaceuticas, Universidade Estadual do Oeste do 
      Parana, Cascavel, Parana, Brazil.
FAU - de Oliveira, Cecilia Maria Alves
AU  - de Oliveira CMA
AD  - Laboratorio de Produtos Naturais, Instituto de Quimica, Universidade Federal de 
      Goias, Goiania, Brazil.
FAU - Kato, Lucilia
AU  - Kato L
AD  - Laboratorio de Produtos Naturais, Instituto de Quimica, Universidade Federal de 
      Goias, Goiania, Brazil.
FAU - Borges, Clayton Luiz
AU  - Borges CL
AD  - Laboratorio de Biologia Molecular, Instituto de Ciencias Biologicas, Universidade 
      Federal de Goias, Goiania, Goias, Brazil.
FAU - de Almeida Soares, Celia Maria
AU  - de Almeida Soares CM
AD  - Laboratorio de Biologia Molecular, Instituto de Ciencias Biologicas, Universidade 
      Federal de Goias, Goiania, Goias, Brazil.
FAU - Pereira, Maristela
AU  - Pereira M
AD  - Laboratorio de Biologia Molecular, Instituto de Ciencias Biologicas, Universidade 
      Federal de Goias, Goiania, Goias, Brazil maristelaufg@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181024
PL  - United States
TA  - Antimicrob Agents Chemother
JT  - Antimicrobial agents and chemotherapy
JID - 0315061
RN  - 0 (Antifungal Agents)
RN  - 0 (Lactones)
RN  - 0 (argentilactone)
RN  - 304NUG5GF4 (Itraconazole)
RN  - 7XU7A7DROE (Amphotericin B)
SB  - IM
MH  - A549 Cells
MH  - Amphotericin B/pharmacology
MH  - Antifungal Agents/*pharmacology
MH  - Brazil
MH  - Cell Line, Tumor
MH  - Cell Wall/drug effects
MH  - Humans
MH  - Itraconazole/pharmacology
MH  - Lactones/*pharmacology
MH  - Paracoccidioides/*drug effects
MH  - Paracoccidioidomycosis/*drug therapy
PMC - PMC6201122
OTO - NOTNLM
OT  - Paracoccidioides
OT  - antifungal
OT  - argentilactone
OT  - chemoproteomics
OT  - drug discovery
OT  - targets
EDAT- 2018/08/29 06:00
MHDA- 2019/10/11 06:00
PMCR- 2019/04/24
CRDT- 2018/08/29 06:00
PHST- 2018/04/18 00:00 [received]
PHST- 2018/08/17 00:00 [accepted]
PHST- 2018/08/29 06:00 [pubmed]
PHST- 2019/10/11 06:00 [medline]
PHST- 2018/08/29 06:00 [entrez]
PHST- 2019/04/24 00:00 [pmc-release]
AID - AAC.00737-18 [pii]
AID - 00737-18 [pii]
AID - 10.1128/AAC.00737-18 [doi]
PST - epublish
SO  - Antimicrob Agents Chemother. 2018 Oct 24;62(11):e00737-18. doi: 
      10.1128/AAC.00737-18. Print 2018 Nov.