Treatment with synthetic lipophilic tyrosyl ester controls Leishmania major infection by reducing parasite load in BALB/c mice

• Published in: Parasitology Vol. 143; no. 12; pp. 1615 - 1621
• Main Authors: SGHAIER, RABIAA M., AISSA, IMEN, ATTIA, HANÈNE, BALI, AYMEN, LEON MARTINEZ, PABLO A., MKANNEZ, GHADA, GUERFALI, FATMA Z., GARGOURI, YOUSSEF, LAOUINI, DHAFER
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 01.10.2016
• Subjects: Animals; Antiprotozoal Agents - administration & dosage; Cytokines - secretion; Cytokines/metabolism; Disease Models, Animal; Immunologic Factors - administration & dosage; Injections, Subcutaneous; Leishmania infantum; Leishmania major; Leishmania major - drug effects; Leishmaniasis, Cutaneous - drug therapy; Life Sciences; Mice; Mice, Inbred BALB C; Microbiology and Parasitology; Parasite Load; Th1 Cells - immunology; Tyrosine - analogs & derivatives; Tyrosine - pharmacology; lipophilic tyrosyl ester; anti-leishmanial activity; parasite load; Leishmania major
• ISSN: 0031-1820; 1469-8161
• DOI: 10.1017/S0031182016001086

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 γ/interleukin 4 (IFN-γ/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-γ 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.