Author: Herr Dr. Amoneit
Last saved by: Saritas, Sevim

Assessment of Synthetic Lipophilic Tyrosyl Ester efficiency against Leishmania parasites
Imen Aissa^1 , Rabiaa Manel Sghaier^2, Aymen Bali^2,  Hanene Attia^2, Sameh Amour,^2Ghada Mkannez^2, Mohamed Sellami^1, Dhafer Laouini^2, Youssef Gargouri^1
1-Laboratoire de Biochimie et de Génie Enzymatique des Lipases, Ecole Nationale d'Ingénieurs de Sfax (ENIS). Université de Sfax,Tunisie.
2- Groupe Immunobiologie des Leishmanioses, Laboratoire de Transmission, Contrôle et Immunobiologie des Infections (LTCII), Institut Pasteur de Tunis, Université Tunis El Manar, Tunisie 
 
Infections caused by protozoa of the genus Leishmania are a major worldwide health problem, with high endemicity in developing countries. Toxicity, cost and resistance are the major limits of leishmaniasis treatment. Therefore, the development of newer drugs from natural sources is needed.
A large series of tyrosyl esters (TyC_2 to TyC_18:1) with increasing lipophilicity was synthesized in a good yield using lipases of Rhizopus oryzae and Staphylococcus xylosus immobilized onto CaCO_3. Synthesized compounds were evaluated for their antileishmanial activity against either Leishmania major or Leishmania infantum parasite species in vitro. In the experimental model of cutaneous L. major Balb/c. In vivo antileishmanial activity was monitored following intralesional injection. The immune response was analyzed by RT-PCR.
Among all the tested compounds, our results showed that only  medium tyrosyl derivatives (TyC_8, TyC_10 and TyC_12) exhibited antileishmanial activities. When IC50 values were plotted against the acyl chain length of each tyrosyl derivative, The curve showed a parabolic shape with a minimum value for TyC_10. This dependency with the increase of the chain length indicates that biological activities are probably associated to the surfactant effectiveness of lipophilic derivatives. Furthermore, the injection of TyC_10 showed a decrease of lesion development and parasite charge, without any significant side-effects. This treatment had activated a protective pro-inflammatory response assigned with an induction of iNOS gene expression.
These results open up potential applications to use medium tyrosyl derivatives as natural drugs with antileishmanial activity.

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