New synthetic molecules incorporated into polymeric micelles used for treatment against visceral leishmaniasis

Freitas C.S.; Pereira I.A.G.; Lage D.P.; Vale D.L.; Pimenta B.L.; Soares N.P.; Santiago S.S.; Martins V.T.; Câmara R.S.B.; Jesus M.M.; Tavares G.S.V.; Ramos F.F.; Ludolf F.; Magalhães L.N.D.; Oliveira F.M.; Duarte M.C.; Chávez-Fumagalli M.A.; Costa A.V.; Roatt B.M.; Teixeira R.R.; Coelho E.A.F. · Cytokine (2024) · DOI: 10.1016/j.cyto.2024.156543

Resumen

Treatment against visceral leishmaniasis (VL) presents problems, mainly related to drug toxicity, high cost and/or by emergence of resistant strains. In the present study, two vanillin synthetic derivatives, 3 s [4-(2-hydroxy-3-(4-octyl-1H-1,2,3-triazol-1-yl)propoxy)-3-methoxybenzaldehyde] and 3 t [4-(3-(4-decyl-1H-1,2,3-triazol-1-yl)-2-hydroxypropoxy)-3-methoxybenzaldehyde], were evaluated as therapeutic candidates in a murine model against Leishmania infantum infection. Molecules were used pure (3 s and 3 t) or incorporated into Poloxamer 407-based micelles (3 s/M and 3 t/M) in the infected animals, which also received amphotericin B (AmpB) or Ambisome® as control. Results showed that 3 s/M and 3 t/M compositions induced a Th1-type immune response in treated animals, with higher levels of IFN-γ, IL-2, TNF-α, IL-12, nitrite, and IgG2a antibodies. Animals presented also low toxicity and significant reductions in the parasite load in their spleens, livers, bone marrows and draining lymph nodes, as compared as control groups mice, with the evaluations performed one and 30 days after the application of the therapeutics. In conclusion, preliminary data suggest that 3 s/M and 3 t/M could be considered for future studies as therapeutic agents against VL.

Instituciones: Universidad Católica de Santa María