title: Click chemistry decoration of amino sterols as promising strategy to developed new leishmanicidal drugs.
abstract: A series of 1,2,3-triazolylsterols was prepared from pregnenolone through reductive amination and copper(I)-catalyzed azide-alkyne cycloaddition (click chemistry). The newly generated stereocenter of the key propargylamino intermediate provided a mixture of diastereomers which were separated chromatographically, and the configuration of the R isomer was determined by X-ray crystallography. Ten triazolyl sterols were prepared, and the products and intermediates were screened in vitro against different parasites, with some compounds presenting IC50 values in the low micromolar range against Leishmania donovani.
authors.affiliation: Instituto de Química Rosario (IQUIR-CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, S2002LRK Rosario, Argentina.
authors.forename: Exequiel O J
authors.initials: EO
authors.lastname: Porta
authors.affiliation: School of Pharmacy, Notre Dame of Maryland University, Baltimore, MD 21210, USA.
authors.forename: Paulo B
authors.initials: PB
authors.lastname: Carvalho
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, University of Mississippi, University, MS 38677, USA.
authors.forename: Mitchell A
authors.initials: MA
authors.lastname: Avery
authors.affiliation: National Center for Natural Products Research & Department of Pharmacology, School of Pharmacy, University of Mississippi, University, MS 38677, USA.
authors.forename: Babu L
authors.initials: BL
authors.lastname: Tekwani
authors.affiliation: Instituto de Química Rosario (IQUIR-CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, S2002LRK Rosario, Argentina. Electronic address: labadie@iquir-conicet.gov.ar.
authors.forename: Guillermo R
authors.initials: GR
authors.lastname: Labadie
mesh_terms: D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D057930:Click Chemistry / Q000379:methods*; D018360:Crystallography, X-Ray; D020128:Inhibitory Concentration 50; D007893:Leishmania donovani / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D015394:Molecular Structure; D010963:Plasmodium falciparum / Q000187:drug effects*; D013261:Sterols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000981:Antiprotozoal Agents; D013261:Sterols
keywords: Antileishmanial; Antimalarial; Click chemistry; Pregnenolone; Reductive amination; Triazolylsterols