title: Synthesis and antileishmanial activity of 3-imidazolylalkylindoles. Part I.
abstract: The present study was designed to investigate conazoles as new antileishmanial agents. Several 3-imidazolylalkyl-indoles were prepared under mild reaction conditions and pharmacomodulation at N1 and C5 of the indole ring and at the level of the alkyl chain (R) was carried out starting from the corresponding 3-formylindoles 7-10. All target imidazolyl compounds 38-52 were evaluated in vitro against Leishmania mexicana promastigotes; ketoconazole, amphotericin B and meglumine antimoniate were used as references. Eight out of fifteen compounds (40,43,44,47,48, 50, 51 and 52) exerted similar activity to ketoconazole, with IC50 values in the range of 2.10-3.30 microg/mL. However the most potent compound, 1-(2-bromobenzyl)-3-(1H-imidazol-1-ylmethyl)-1H-indole (38), exhibited IC50 value (0.011+/-0.003 microg/mL) 270-fold lower than that of ketoconazole. Four compounds (38, 43, 50 and 52) were also tested against intracellular amastigotes of L. mexicana; compound 38 exhibited the highest activity with an IC50 value of 0.018+/-0.004 microg/mL.
authors.affiliation: Yang Ji Chemical Co Ltd, Ansan, 425-110 Kyoungki-do, South Korea.
authors.forename: Young Min
authors.initials: YM
authors.lastname: Na
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lebouvier
authors.forename: Marc
authors.initials: M
authors.lastname: Le Borgne
authors.forename: Fabrice
authors.initials: F
authors.lastname: Pagniez
authors.forename: Nidia
authors.initials: N
authors.lastname: Alvarez
authors.forename: Patrice
authors.initials: P
authors.lastname: Le Pape
authors.forename: Guillaume
authors.initials: G
authors.lastname: Le Baut
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology; D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007654:Ketoconazole / Q000494:pharmacology; D007894:Leishmania mexicana / Q000187:drug effects*; D017737:Macrophages, Peritoneal / Q000469:parasitology; D008536:Meglumine / Q000494:pharmacology; D000077485:Meglumine Antimoniate; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000494:pharmacology; D021261:Parasitic Sensitivity Tests; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000981:Antiprotozoal Agents; D007211:Indoles; D009942:Organometallic Compounds; D008536:Meglumine; D000077485:Meglumine Antimoniate; D000666:Amphotericin B; D007654:Ketoconazole