title: Effect of 3-alkylpyridine marine alkaloid analogues in Leishmania species related to American cutaneous leishmaniasis.
abstract: A series of oxygenated analogues of marine 3-alkylpyridine alkaloids were synthesized, and their leishmanicidal activity was assayed. All compounds were prepared from 3-pyridinepropanol in few steps and in good yields. The key step for the synthesis of these compounds was a classic Williamson etherification under phase-transfer conditions. Besides toxicity in peritoneal macrophages, the compounds exhibited a significant leishmanicidal activity. Of twelve compounds tested, five showed a strong leishmanicidal activity against promastigote forms of Leishmania amazonensis and L. braziliensis with IC50 below 10 μm. Compounds 11, 14, 15, and 16 showed a strong leishmanicidal activity on intracellular amastigotes (IC50 values of 2.78; 0.27; 1.03, and 1.33 μm, respectively), which is unlikely to be owing to the activation of nitric oxide production by macrophages.
authors.affiliation: Departamento de Parasitologia, Microbiologia e Imunologia, Instituto de Ciências Biológicas; Universidade Federal de Juiz de Fora, Juiz de Fora, Minas Gerais, Brasil.
authors.forename: Patrícia A
authors.initials: PA
authors.lastname: Machado
authors.forename: Flaviane F
authors.initials: FF
authors.lastname: Hilário
authors.forename: Lidiane O
authors.initials: LO
authors.lastname: Carvalho
authors.forename: Mariana L T
authors.initials: ML
authors.lastname: Silveira
authors.forename: Rosemeire B
authors.initials: RB
authors.lastname: Alves
authors.forename: Rossimiriam P
authors.initials: RP
authors.lastname: Freitas
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Coimbra
mesh_terms: D000470:Alkaloids / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D002478:Cells, Cultured; D006801:Humans; D020128:Inhibitory Concentration 50; D007891:Leishmania / Q000187:drug effects*; D007896:Leishmaniasis / Q000188:drug therapy; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000378:metabolism; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity
chemical_list: D000470:Alkaloids; D000981:Antiprotozoal Agents; D011725:Pyridines; D009569:Nitric Oxide