title: Synthesis and antiprotozoal activity of oligomethylene- and  p-phenylene-bis(methylene)-linked bis(+)-huprines.
abstract: We have synthesized a series of dimers of (+)-(7R,11R)-huprine Y and evaluated their activity against Trypanosoma brucei, Plasmodium falciparum, rat myoblast L6 cells and human acetylcholinesterase (hAChE), and their brain permeability. Most dimers have more potent and selective trypanocidal activity than huprine Y and are brain permeable, but they are devoid of antimalarial activity and remain active against hAChE. Lead optimization will focus on identifying compounds with a more favourable trypanocidal/anticholinesterase activity ratio.
authors.forename: Irene
authors.initials: I
authors.lastname: Sola
authors.forename: Albert
authors.initials: A
authors.lastname: Artigas
authors.forename: Martin C
authors.initials: MC
authors.lastname: Taylor
authors.forename: Stephen Y
authors.initials: SY
authors.lastname: Gbedema
authors.forename: Belén
authors.initials: B
authors.lastname: Pérez
authors.forename: M Victòria
authors.initials: MV
authors.lastname: Clos
authors.forename: Colin W
authors.initials: CW
authors.lastname: Wright
authors.forename: John M
authors.initials: JM
authors.lastname: Kelly
authors.forename: Diego
authors.initials: D
authors.lastname: Muñoz-Torrero
mesh_terms: D000962:Antimalarials / Q000494:pharmacology*; D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D000981:Antiprotozoal Agents