PMID- 27312247
OWN - NLM
STAT- MEDLINE
DCOM- 20170823
LR  - 20181202
IS  - 1469-8161 (Electronic)
IS  - 0031-1820 (Linking)
VI  - 143
IP  - 12
DP  - 2016 Oct
TI  - Treatment with synthetic lipophilic tyrosyl ester controls Leishmania major 
      infection by reducing parasite load in BALB/c mice.
PG  - 1615-21
LID - 10.1017/S0031182016001086 [doi]
AB  - Synthesized lipophilic tyrosyl ester derivatives with increasing lipophilicity 
      were effective against Leishmania (L.) major and Leishmania infantum species in 
      vitro. These findings prompted us to test in vivo leishmanicidal properties of 
      these molecules and their potential effect on the modulation of immune responses. 
      The experimental BALB/c model of cutaneous leishmaniasis was used in this study. 
      Mice were infected with L. major parasites and treated with three in vitro active 
      tyrosyl esters derivatives. Among these tested tyrosylcaprate (TyC) compounds, 
      only TyC10 exhibited an in vivo anti-leishmanial activity, when injected 
      sub-cutaneously (s.c.). TyC10 treatment of L. major-infected BALB/c mice resulted 
      in a decrease of lesion development and parasite load. TyC10 s.c. treatment of 
      non-infected mice induced an imbalance in interferon gamma/interleukin 4 (IFN-gamma/IL-4) 
      ratio cytokines towards a Th1 response. Our results indicate that TyC10 s.c. 
      treatment improves lesions' healing and parasite clearance and may act on the 
      cytokine balance towards a Th1 protective response by decreasing IL-4 and 
      increasing IFN-gamma transcripts. TyC10 is worthy of further investigation to uncover 
      its mechanism of action that could lead to consider this molecule as a potential 
      drug candidate.
FAU - Sghaier, Rabiaa M
AU  - Sghaier RM
AD  - Laboratory of Transmission, Control and Immunobiology of Infections 
      (LTCII),Institut Pasteur de Tunis,LR11IPT02, Tunis-Belvedere, 1002,Tunisia.
FAU - Aissa, Imen
AU  - Aissa I
AD  - Laboratoire de Biochimie et de Genie Enzymatique des Lipases,Ecole Nationale 
      d'Ingenieurs de Sfax (ENIS), Universite de Sfax,Route de Soukra,BP 1173, 3038 
      Sfax,Tunisie.
FAU - Attia, Hanene
AU  - Attia H
AD  - Laboratory of Transmission, Control and Immunobiology of Infections 
      (LTCII),Institut Pasteur de Tunis,LR11IPT02, Tunis-Belvedere, 1002,Tunisia.
FAU - Bali, Aymen
AU  - Bali A
AD  - Laboratory of Transmission, Control and Immunobiology of Infections 
      (LTCII),Institut Pasteur de Tunis,LR11IPT02, Tunis-Belvedere, 1002,Tunisia.
FAU - Leon Martinez, Pablo A
AU  - Leon Martinez PA
AD  - Laboratory of Transmission, Control and Immunobiology of Infections 
      (LTCII),Institut Pasteur de Tunis,LR11IPT02, Tunis-Belvedere, 1002,Tunisia.
FAU - Mkannez, Ghada
AU  - Mkannez G
AD  - Laboratory of Transmission, Control and Immunobiology of Infections 
      (LTCII),Institut Pasteur de Tunis,LR11IPT02, Tunis-Belvedere, 1002,Tunisia.
FAU - Guerfali, Fatma Z
AU  - Guerfali FZ
AD  - Laboratory of Transmission, Control and Immunobiology of Infections 
      (LTCII),Institut Pasteur de Tunis,LR11IPT02, Tunis-Belvedere, 1002,Tunisia.
FAU - Gargouri, Youssef
AU  - Gargouri Y
AD  - Laboratoire de Biochimie et de Genie Enzymatique des Lipases,Ecole Nationale 
      d'Ingenieurs de Sfax (ENIS), Universite de Sfax,Route de Soukra,BP 1173, 3038 
      Sfax,Tunisie.
FAU - Laouini, Dhafer
AU  - Laouini D
AD  - Laboratory of Transmission, Control and Immunobiology of Infections 
      (LTCII),Institut Pasteur de Tunis,LR11IPT02, Tunis-Belvedere, 1002,Tunisia.
LA  - eng
PT  - Journal Article
DEP - 20160617
PL  - England
TA  - Parasitology
JT  - Parasitology
JID - 0401121
RN  - 0 (Antiprotozoal Agents)
RN  - 0 (Cytokines)
RN  - 0 (Immunologic Factors)
RN  - 42HK56048U (Tyrosine)
SB  - IM
MH  - Animals
MH  - Antiprotozoal Agents/*administration & dosage
MH  - Cytokines/metabolism
MH  - Disease Models, Animal
MH  - Immunologic Factors/*administration & dosage
MH  - Injections, Subcutaneous
MH  - Leishmania major/*drug effects
MH  - Leishmaniasis, Cutaneous/*drug therapy
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Parasite Load
MH  - Th1 Cells/immunology
MH  - Tyrosine/analogs & derivatives/pharmacology
OTO - NOTNLM
OT  - Leishmania major
OT  - anti-leishmanial activity
OT  - lipophilic tyrosyl ester
OT  - parasite load
EDAT- 2016/06/18 06:00
MHDA- 2017/08/24 06:00
CRDT- 2016/06/18 06:00
PHST- 2016/06/18 06:00 [entrez]
PHST- 2016/06/18 06:00 [pubmed]
PHST- 2017/08/24 06:00 [medline]
AID - S0031182016001086 [pii]
AID - 10.1017/S0031182016001086 [doi]
PST - ppublish
SO  - Parasitology. 2016 Oct;143(12):1615-21. doi: 10.1017/S0031182016001086. Epub 2016 
      Jun 17.