title: In vitro activity of scorpiand-like azamacrocycle derivatives in promastigotes and intracellular amastigotes of Leishmania infantum and Leishmania braziliensis.
abstract: The activity of a family scorpiand-like azamacrocycles against Leishmania infantum and Leishmania braziliensis was studied using promastigotes, axenic and intracellular amastigotes forms. All the compounds are more active and less toxic than meglumine antimoniate (Glucantime). Moreover, the data on infection rates and amastigotes showed that compounds P2Py, PN and P3Py are the most active against both species of Leishmania. On the other hand, studies on the inhibitory effect of these compounds on SOD enzymes showed that while the inhibition of the Fe-SOD enzyme of the promastigote forms of the parasites is remarkable, the inhibition of human CuZn-SOD and Mn-SOD from Escherichia coli is negligible. The ultrastructural alterations observed in treated promastigote forms confirmed that the compounds having the highest activity were those causing the largest cell damage. The modifications observed by (1)H NMR, and the amounts of catabolites excreted by the parasites after treatment with the compounds, suggested that the catabolic mechanism could depend on the structure of the side chains linked to the aza-scorpiand macrocycles.
authors: Departamento de Parasitología, Facultad de Ciencias, Universidad de Granada, E-18071 Granada, Spain. cmaris@ugr.es
authors: Clotilde
authors: C
authors: Marín
authors: M Paz
authors: MP
authors: Clares
authors: Inmaculada
authors: I
authors: Ramírez-Macías
authors: Salvador
authors: S
authors: Blasco
authors: Francisco
authors: F
authors: Olmo
authors: Conxa
authors: C
authors: Soriano
authors: Begoña
authors: B
authors: Verdejo
authors: María José
authors: MJ
authors: Rosales
authors: David
authors: D
authors: Gomez-Herrera
authors: Enrique
authors: E
authors: García-España
authors: Manuel
authors: M
authors: Sánchez-Moreno
mesh_terms: D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001372:Aza Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007892:Leishmania braziliensis / Q000187:drug effects*; D018314:Leishmania infantum / Q000187:drug effects*; D047028:Macrocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D013329:Structure-Activity Relationship
chemical_list: D000981:Antiprotozoal Agents; D001372:Aza Compounds; D047028:Macrocyclic Compounds