PMID- 29945180
OWN - NLM
STAT- MEDLINE
DCOM- 20190404
LR  - 20190404
IS  - 1460-2709 (Electronic)
IS  - 1369-3786 (Linking)
VI  - 57
IP  - 3
DP  - 2019 Apr 1
TI  - Thiosemicarbazone of lapachol acts on cell membrane in Paracoccidioides 
      brasiliensis.
PG  - 332-339
LID - 10.1093/mmy/myy045 [doi]
AB  - Paracoccidioidomycosis (PCM) is the most prevalent systemic mycosis in Latin 
      American countries. Amphotericin B, sulfonamides, and azoles may be used in the 
      treatment of PCM. However, the high toxicity, prolonged course of treatment, and 
      significant frequency of disease relapse compromise their use. Therefore, there 
      is a need to seek new therapeutic options. We conducted tests with 
      thiosemicarbazone of lapachol (TSC-lap) to determine the antifungal activity and 
      phenotypic effects against several isolates of Paracoccidioides spp. In addition, 
      we evaluated the toxicity against murine macrophages and the ability to enhance 
      phagocytosis. Further, we verified that TSC-lap was active against yeasts but did 
      not show any interaction with the drugs tested. The TSC-lap showed no toxicity at 
      the concentration of 40 mug/ml in macrophages, and at 15.6 mug/ml it could increase 
      the phagocytic index. We observed that this compound induced in vitro 
      ultrastructural changes manifested as withered and broken cells beyond a 
      disorganized cytoplasm with accumulation of granules. We did not observe 
      indications of activity in the cell wall, although membrane damages were noted. 
      We observed alterations in the membrane permeability, culminating in a 
      significant increase in K+ efflux and a gradual loss of the cellular content with 
      increase in the concentration of TSC-lap. In addition, we showed a significant 
      reduction of ergosterol amount in the Pb18 membrane. These data reinforce the 
      possible mechanism of action of this compound to be closely associated with 
      ergosterol biosynthesis and reaffirms the antifungal potential of TSC-lap against 
      Paracoccidioides spp.
CI  - (c) The Author(s) 2018. Published by Oxford University Press on behalf of The 
      International Society for Human and Animal Mycology.
FAU - de Sa, Nivea Pereira
AU  - de Sa NP
AD  - Departamento de Microbiologia, Instituto de Ciencias Biologicas, Universidade 
      Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
FAU - Cisalpino, Patricia Silva
AU  - Cisalpino PS
AD  - Departamento de Microbiologia, Instituto de Ciencias Biologicas, Universidade 
      Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
FAU - Bertollo, Caryne Margotto
AU  - Bertollo CM
AD  - Laboratory of Chemistry of Natural Products, Rene Rachou Research Center, 
      FIOCRUZ, Belo Horizonte, MG, Brazil.
FAU - Santos, Patricia Campi
AU  - Santos PC
AD  - Departamento de Microbiologia, Instituto de Ciencias Biologicas, Universidade 
      Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
FAU - Rosa, Carlos Augusto
AU  - Rosa CA
AD  - Departamento de Microbiologia, Instituto de Ciencias Biologicas, Universidade 
      Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
FAU - de Souza, Daniele da Gloria
AU  - de Souza DDG
AD  - Departamento de Microbiologia, Instituto de Ciencias Biologicas, Universidade 
      Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
FAU - Barbeira, Paulo Jorge Sanches
AU  - Barbeira PJS
AD  - Departamento de Quimica, Instituto de Ciencias Exatas, Universidade Federal de 
      Minas Gerais, Belo Horizonte, MG, Brazil.
FAU - Alves, Tania Maria de Almeida
AU  - Alves TMA
AD  - Laboratory of Chemistry of Natural Products, Rene Rachou Research Center, 
      FIOCRUZ, Belo Horizonte, MG, Brazil.
FAU - Zani, Carlos Leomar
AU  - Zani CL
AD  - Laboratory of Chemistry of Natural Products, Rene Rachou Research Center, 
      FIOCRUZ, Belo Horizonte, MG, Brazil.
FAU - Johann, Susana
AU  - Johann S
AD  - Departamento de Microbiologia, Instituto de Ciencias Biologicas, Universidade 
      Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
LA  - eng
PT  - Journal Article
PL  - England
TA  - Med Mycol
JT  - Medical mycology
JID - 9815835
RN  - 0 (Antifungal Agents)
RN  - 0 (Naphthoquinones)
RN  - 0 (Thiosemicarbazones)
RN  - B221938VB6 (lapachol)
RN  - Z30RAY509F (Ergosterol)
SB  - IM
MH  - Animals
MH  - Antifungal Agents/*pharmacology
MH  - Cell Membrane/*drug effects
MH  - Ergosterol/biosynthesis
MH  - Macrophages/drug effects
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Microbial Sensitivity Tests
MH  - Naphthoquinones/*pharmacology
MH  - Paracoccidioides/*drug effects
MH  - Paracoccidioidomycosis/drug therapy/microbiology
MH  - Phagocytosis/drug effects
MH  - Thiosemicarbazones/*pharmacology
OTO - NOTNLM
OT  - Paracoccidioides
OT  - Antifungal
OT  - ergosterol
OT  - thiosemicarbazone of lapachol
EDAT- 2018/06/27 06:00
MHDA- 2019/04/05 06:00
CRDT- 2018/06/27 06:00
PHST- 2017/10/08 00:00 [received]
PHST- 2018/04/23 00:00 [revised]
PHST- 2018/06/27 06:00 [pubmed]
PHST- 2019/04/05 06:00 [medline]
PHST- 2018/06/27 06:00 [entrez]
AID - 5045352 [pii]
AID - 10.1093/mmy/myy045 [doi]
PST - ppublish
SO  - Med Mycol. 2019 Apr 1;57(3):332-339. doi: 10.1093/mmy/myy045.