title: Activity and mode of action of acridine compounds against Leishmania donovani.
abstract: In the present work, we have assayed both the in vitro and in vivo action of two acridine compounds against Leishmania donovani. As part of this effort, we have studied the possible action mechanism of these compounds at the ultrastructural and biochemical levels and in relation to the synthesis of macromolecules. The two acridinones inhibit the in vitro growth of the promastigote forms of L. donovani at the highest concentration assayed (100 micrograms/ml). The in vivo results indicate that both compounds reduce the number of amastigotes per gram of spleen, and decrease parasitism, by more than 40%. With respect to the action mechanism, both compounds inhibit the incorporation of [3H]thymidine, inducing alterations at the ultrastructural level in the DNA and mitochondria. Alterations are also caused in the enzymes of the Krebs cycle.
authors.affiliation: Departamento de Biología Aplicada, Universidad de Almeria, Spain.
authors.forename: C M
authors.initials: CM
authors.lastname: Mesa-Valle
authors.forename: J
authors.initials: J
authors.lastname: Castilla-Calvente
authors.forename: M
authors.initials: M
authors.lastname: Sanchez-Moreno
authors.forename: V
authors.initials: V
authors.lastname: Moraleda-Lindez
authors.forename: J
authors.initials: J
authors.lastname: Barbe
authors.forename: A
authors.initials: A
authors.lastname: Osuna
mesh_terms: D000166:Acridines / Q000494:pharmacology*; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D007893:Leishmania donovani / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D007898:Leishmaniasis, Visceral / Q000469:parasitology; D008264:Macrophages / Q000469:parasitology; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008807:Mice, Inbred BALB C; D009696:Nucleic Acids / Q000032:analysis / Q000096:biosynthesis; D014176:Protein Biosynthesis; D011506:Proteins / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000469:parasitology
chemical_list: D000166:Acridines; D000981:Antiprotozoal Agents; C102544:BG 325; C102545:BG 374; D009696:Nucleic Acids; D011506:Proteins