title: In vitro activity of synthetic tetrahydroindeno[2,1-c]quinolines on Leishmania mexicana.
abstract: New synthetic compounds based on tetrahydroindenoquinoline structure were evaluated for their in vitro antileishmanial activities. The seven compounds assayed have antiproliferative activities against promastigotes of Leishmania mexicana. Compound 1 and 3 were the most active (IC50 1.0 μg/ml) and showed high selectivity towards the parasite. These compounds were selected to evaluate their effect on promastigote morphology and mitochondrial transmembrane potential as well as on the amastigote capability to survive into macrophages J774 cell line. Whereas compound 1 affected the promastigote cell cycle, compound 3 induced morphological changes and the total collapse of the mitochondrial transmembrane potential, a hallmark of apoptosis. Both compounds also affected the amastigote form of the parasite, decreasing their survival rate in J774 macrophages. Due to the greatest selectivity index, the apparent effect as apoptotic inducer and its sustained inhibition on intracellular amastigote replication, compound 3 is the best candidate to be tested in vivo. This compound is worth considering for the development of new antileishmanial drugs.
authors.affiliation: Laboratorio de Fisiología de Membranas, Instituto de Biología Experimental, Facultad de Ciencias, Universidad Central de Venezuela, Apartado 47114, Caracas 1041A, Venezuela. Electronic address: hernandezchinea@yahoo.com.
authors.forename: Concepción
authors.initials: C
authors.lastname: Hernández-Chinea
authors.affiliation: Laboratorio de Fisiología de Membranas, Instituto de Biología Experimental, Facultad de Ciencias, Universidad Central de Venezuela, Apartado 47114, Caracas 1041A, Venezuela.
authors.forename: Erika
authors.initials: E
authors.lastname: Carbajo
authors.affiliation: Centro de Biociencias, Area Salud, Fundación Instituto de Estudios Avanzados-IDEA, Edo. Miranda, Venezuela.
authors.forename: Felipe
authors.initials: F
authors.lastname: Sojo
authors.affiliation: Centro de Biociencias, Area Salud, Fundación Instituto de Estudios Avanzados-IDEA, Edo. Miranda, Venezuela; Laboratorio de Cultivo de Tejidos y Biología de Tumores, Instituto de Biología Experimental, Facultad de Ciencias, Universidad Central de Venezuela, Caracas 1041A, Venezuela.
authors.forename: Francisco
authors.initials: F
authors.lastname: Arvelo
authors.affiliation: Laboratorio de Química Orgánica y Biomolecular, Escuela de Química, Universidad Industrial de Santander, AA 678 Bucaramanga Colombia.
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Kouznetsov
authors.affiliation: Laboratorio de Química Orgánica y Biomolecular, Escuela de Química, Universidad Industrial de Santander, AA 678 Bucaramanga Colombia.
authors.forename: Arnold R
authors.initials: AR
authors.lastname: Romero-Bohórquez
authors.affiliation: Laboratorio de Fisiología de Membranas, Instituto de Biología Experimental, Facultad de Ciencias, Universidad Central de Venezuela, Apartado 47114, Caracas 1041A, Venezuela.
authors.forename: Pedro J
authors.initials: PJ
authors.lastname: Romero
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D006801:Humans; D007192:Indenes / Q000494:pharmacology*; D007894:Leishmania mexicana / Q000187:drug effects*; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy*; D008264:Macrophages / Q000276:immunology / Q000469:parasitology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D021261:Parasitic Sensitivity Tests; D011804:Quinolines / Q000494:pharmacology*
chemical_list: D000981:Antiprotozoal Agents; D007192:Indenes; D011804:Quinolines
keywords: Antileishmanial drugs; Indenoquinoline; Leishmania mexicana; Promastigote