title: Inhibition of Leishmania mexicana Growth by the Tuberculosis Drug SQ109.
abstract: We report that the tuberculosis drug SQ109 [N-adamantan-2-yl-N'-((E)-3,7-dimethyl-octa-2,6-dienyl)-ethane-1,2-diamine] has potent activity against the intracellular amastigote form of Leishmania mexicana (50% inhibitory concentration [IC50], ∼11 nM), with a good selectivity index (>500). It is also active against promastigotes (IC50, ∼500 nM) and acts as a protonophore uncoupler, in addition to disrupting Ca(2+) homeostasis by releasing organelle Ca(2+) into the cytoplasm, and as such, it is an interesting new leishmaniasis drug hit candidate.
authors.affiliation: Instituto de Estudios Avanzados, Caracas, Venezuela Instituto de Biología Experimental, Facultad de Ciencias, Universidad Central de Venezuela (UCV), Caracas, Venezuela.
authors.forename: Verónica
authors.initials: V
authors.lastname: García-García
authors.affiliation: Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA eoldfiel@illinois.edu gbenaim@idea.gob.ve.
authors.forename: Eric
authors.initials: E
authors.lastname: Oldfield
authors.affiliation: Instituto de Estudios Avanzados, Caracas, Venezuela Instituto de Biología Experimental, Facultad de Ciencias, Universidad Central de Venezuela (UCV), Caracas, Venezuela eoldfiel@illinois.edu gbenaim@idea.gob.ve.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Benaim
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D000995:Antitubercular Agents; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005029:Ethylenediamines / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D007894:Leishmania mexicana / Q000187:drug effects* / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000469:parasitology; D051379:Mice
chemical_list: D000981:Antiprotozoal Agents; D000995:Antitubercular Agents; D005029:Ethylenediamines; C506841:N-geranyl-N'-(2-adamantyl)ethane-1,2-diamine; D000218:Adamantane; D002118:Calcium