title: Synthesis and antileishmanial activities of 4,5-di-substituted acridines as compared to their 4-mono-substituted homologues.
abstract: Newly synthesized 4,5-di-substituted acridines were assessed for in vitro antileishmanial activities as compared to those of their 4-mono-substituted homologues. Mono-substituted acridines exhibited a weak specificity for Leishmania parasites. Di-substituted acridines, on the contrary, displayed interesting amastigote-specific activities through a mechanism of action that might not involve intercalation to DNA. This antileishmanial property, associated with a low antiproliferative activity towards human cells, led to the identification of a new class of promising acridine derivatives such as 4,5-bis(hydroxymethyl)acridine with a nonclassical mechanism of action based on the inhibition of Leishmania internalization within macrophages. In the meantime, the effects of experimental lighting on the biological properties of acridines were assessed: experimental lighting did not significantly improve the antileishmanial activity of the compounds since it produced a greater toxicity against human cells.
authors.affiliation: Laboratoire de Parasitologie, Hygiène et Zoologie, Faculté de Pharmacie, 27 Bd. Jean Moulin, 13385 Marseille Cedex 05, France. carole.digiorgio@pharmacie.univ-mrs.fr
authors.forename: Di Giorgio
authors.initials: DG
authors.lastname: Carole
authors.forename: De Méo
authors.initials: DM
authors.lastname: Michel
authors.forename: Chiron
authors.initials: C
authors.lastname: Julien
authors.forename: Delmas
authors.initials: D
authors.lastname: Florence
authors.forename: Nikoyan
authors.initials: N
authors.lastname: Anna
authors.forename: Jean
authors.initials: J
authors.lastname: Séverine
authors.forename: Dumenil
authors.initials: D
authors.lastname: Gérard
authors.forename: Timon-David
authors.initials: TD
authors.lastname: Pierre
authors.forename: Galy
authors.initials: G
authors.lastname: Jean-Pierre
mesh_terms: D000166:Acridines / Q000138:chemical synthesis* / Q000145:classification / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007891:Leishmania / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects / Q000469:parasitology; D015394:Molecular Structure; D009000:Monocytes / Q000187:drug effects / Q000469:parasitology; D021261:Parasitic Sensitivity Tests; D013045:Species Specificity
chemical_list: D000166:Acridines