Parasitological and immunological evaluation of a novel chemotherapeutic agent against visceral leishmaniasis

Pereira I.A.G.; Mendonça D.V.C.; Tavares G.S.V.; Lage D.P.; Ramos F.F.; Oliveira-da-Silva J.A.; Antinarelli L.M.R.; Machado A.S.; Carvalho L.M.; Carvalho A.M.R.S.; Salustiano I.V.; Reis T.A.R.; Bandeira R.S.; Silva A.M.; Martins V.T.; Chávez-Fumagalli M.A.; Humbert M.V.; Roatt B.M.; Duarte M.C.; Menezes-Souza D.; Coimbra E.S.; Leite J.P.V.; Coelho E.A.F.; Gonçalves D.U. · Parasite Immunology (2020) · DOI: 10.1111/pim.12784

Resumen

Aims: Treatment for visceral leishmaniasis (VL) is hampered by the toxicity and/or high cost of drugs, as well as by emergence of parasite resistance. Therefore, there is an urgent need for new antileishmanial agents. Methods and Results: In this study, the antileishmanial activity of a diprenylated flavonoid called 5,7,3,4’-tetrahydroxy-6,8-diprenylisoflavone (CMt) was tested against Leishmania infantum and L amazonensis species. Results showed that CMt presented selectivity index (SI) of 70.0 and 165.0 against L infantum and L amazonensis promastigotes, respectively, and of 181.9 and 397.8 against respective axenic amastigotes. Amphotericin B (AmpB) showed lower SI values of 9.1 and 11.1 against L infantum and L amazonensis promastigotes, respectively, and of 12.5 and 14.3 against amastigotes, respectively. CMt was effective in the treatment of infected macrophages and caused alterations in the parasite mitochondria. L infantum-infected mice treated with miltefosine, CMt alone or incorporated in polymeric micelles (CMt/Mic) presented significant reductions in the parasite load in distinct organs, when compared to the control groups. An antileishmanial Th1-type cellular and humoral immune response were developed one and 15 days after treatment, with CMt/Mic-treated mice presenting a better protective response. Conclusion: Our data suggest that CMt/Mic could be evaluated as a chemotherapeutic agent against VL.

Instituciones: Universidad Católica de Santa María