title: Anti-leishmanial evaluation of C2-aryl quinolines: mechanistic insight on bioenergetics and sterol biosynthetic pathway of Leishmania braziliensis.
abstract: A series of diverse simple C2-aryl quinolines was synthesized de novo via a straightforward synthesis based on the acid-catalyzed multicomponent imino Diels-Alder reactions. Seven selected quinolines were evaluated at different stages of Leishmania braziliensis parasite. Among them, the 6-ethyl-2-phenylquinoline 5f was able to inhibit the growth of promastigotes of this parasite without affecting the mammalian cells viability and decreasing the number of intracellular L. braziliensis amastigotes on BMDM macrophages. The mechanism of action studied for the selected compound consisted in: (1) alteration of parasite bioenergetics, by disrupting mitochondrial electrochemical potential and alkalinization of acidocalcisomes, and (2) inhibition of ergosterol biosynthetic pathway in promastigote forms. These results validate the efficiency of quinoline molecules as leishmanicide compounds.
authors.affiliation: Laboratorio de Señalización Celular y Bioquímica de Parásitos, Área de Salud, Instituto de Estudios Avanzados (IDEA), Caracas, Bolivarian Republic of Venezuela.
authors.forename: Daznia
authors.initials: D
authors.lastname: Bompart
authors.forename: Jorge
authors.initials: J
authors.lastname: Núñez-Durán
authors.forename: Daniel
authors.initials: D
authors.lastname: Rodríguez
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Kouznetsov
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Meléndez Gómez
authors.forename: Felipe
authors.initials: F
authors.lastname: Sojo
authors.forename: Francisco
authors.initials: F
authors.lastname: Arvelo
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Visbal
authors.forename: Alvaro
authors.initials: A
authors.lastname: Alvarez
authors.forename: Xenón
authors.initials: X
authors.lastname: Serrano-Martín
authors.forename: Yael
authors.initials: Y
authors.lastname: García-Marchán
mesh_terms: D000818:Animals; D000977:Antiparasitic Agents / Q000737:chemistry / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects; D007892:Leishmania braziliensis / Q000187:drug effects*; D008018:Life Cycle Stages / Q000187:drug effects; D008264:Macrophages / Q000469:parasitology; D015394:Molecular Structure; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000977:Antiparasitic Agents; D011804:Quinolines