Péptidos antimicrobianos y su efecto en el desarrollo de formas parasitarias de leishmania

Abstract

En este estudio se sintetizaron 16 péptidos antimicrobianos de origen natural, evaluándose su efecto sobre las células J774, U937, monocitos de sangre periférica humana, HeLa y HepG2, hematíes y actividad antileishmanial en promastigotes de L. (V.) panamensis y L. (L.) major. Melitina, Bombinina, Mastoparán 8 (MP-8), MP-X y Dermaseptina S1 disminuyeron la viabilidad de los monocitos/macrófagos a mayores concentraciones (CI50 de 20.9 a 49.9 µg/mL) que el isotionato de Pentamidina (CI50, de 3.4 a 20.5 µg/mL). Melitina, Bombinina, Dermaseptina S1, MP-8 y Péptido antimicrobiano traqueal (TAP) fueron los más efectivos sobre la forma de promastigotes de L. (V.) panamensis (CE50 entre 7.6 y 46.3 µg/mL) y L. (L.) major (CE50 entre 6.3 y 42.1 µg/mL), con selectividad de Polistes Mastoparán (MA) y Taquiplesina I en L. (L.) major. Se seleccionaron como promisorios con índice de selectividad (IS) 1 y concentración hemolítica 50 superior a 50 µg/mL a MP-8, Bombinina, Dermaseptina S1 y TAP activos sobre ambas especies del parásito y a Taquiplesina I y Polistes MA selectivamente sobre L. (L.) major./Abstract. In this study we synthesized 16 naturally occurring antimicrobial peptides, evaluating their effect on J774, U937, human peripheral blood monocytes, HeLa and HepG2 cells. Assays for hemolytic and antileishmanial activity on promastigotes of L. (V.) panamensis and L. (L.) major were conducted. Melittin, Bombinin, Mastoparan 8 (MP-8), MP-X and Dermaseptin S1 were able of decreasing the viability of monocytes/macrophages at higher concentrations (IC 50 of 20.9 to 49.9 mg / mL) regarding Pentamidine isothionate (IC50 of 3.4 to 20.5 mg / mL). Melittin, Bombinin, Dermaseptin S1, MP-8 and tracheal antimicrobial peptide (TAP) were the most effective peptides on promastigotes of L. (V.) panamensis (EC50 between 7.6 and 46.3 ug/mL) and L. (L.) major (EC50 between 6.3 and 42.1 ug / mL). Polistes Mastoparan (MA) showing selectivity as well as tachyplesin I on L. (L.) major. These later were selected as promising taking into account their Selectivity Index (SI) 1 and hemolytic concentration HC 50 higher than 50 mg / mL for MP-8, Bombinin, Dermaseptin S1 and TAP respect to both parasite species and peptides Tachyplesin I and Polistes MA displaying selectivity for L. (L.) major.