title: In vitro activities of 7-substituted 9-chloro and 9-amino-2-methoxyacridines and their bis- and tetra-acridine complexes against Leishmania infantum.
abstract: 9-Chloro and 9-amino-2-methoxyacridines bearing different substituents in position 7, as well as their corresponding unsubstituted dimeric and tetrameric complexes, were investigated for in vitro antiproliferative properties against Leishmania infantum compared to toxicity towards human monocytes. The results clearly confirmed that several compounds of the 2-methoxyacridine series, together with their corresponding dimeric and tetrameric derivatives, had strong in vitro antiparasitic properties. Antileishmanial activity was shown to depend on the nature of both 7- and 9-substituted groups in monoacridines, while it varied according to the nature of the 9-substituted group and the length of the linker among bis- and tetra-acridines. The effects of acridine derivatives on DNA synthesis raised the hypothesis that DNA metabolism constituted their main target in Leishmania promastigotes; however, secondary effects on other biochemical pathways, including protein and lipid metabolism, were observed, suggesting that acridine compounds could be considered multitarget drugs.
authors.affiliation: Laboratoire de Parasitologie, Hygiène et Zoologie, Faculté de Pharmacie, Marseille, France. Carole.Digiorgio@Pharmacie.univ-mrs.fr
authors.forename: Carole
authors.initials: C
authors.lastname: Di Giorgio
authors.forename: Florence
authors.initials: F
authors.lastname: Delmas
authors.forename: Nathalie
authors.initials: N
authors.lastname: Filloux
authors.forename: Maxime
authors.initials: M
authors.lastname: Robin
authors.forename: Laetitia
authors.initials: L
authors.lastname: Seferian
authors.forename: Nadine
authors.initials: N
authors.lastname: Azas
authors.forename: Monique
authors.initials: M
authors.lastname: Gasquet
authors.forename: Muriel
authors.initials: M
authors.lastname: Costa
authors.forename: Pierre
authors.initials: P
authors.lastname: Timon-David
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Galy
mesh_terms: D000166:Acridines / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D006801:Humans; D018314:Leishmania infantum / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D009000:Monocytes / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000166:Acridines