title: β-Lapachone analogs with enhanced antiproliferative activity.
abstract: In this study, we describe the synthesis of a series of α- and β-lapachone containing hydroxyl or methoxyl groups on the benzene ring, by means of the selective acid promoted cyclization of the appropriate lapachol analog. The evaluation of the antiproliferative activity in human solid tumor cell lines provided 7-hydroxy-β-lapachone as lead with enhanced activity over the parent drug β-lapachone. Cell cycle studies, protein expression experiments, and reactive oxygen species analysis revealed that, similarly to β-lapachone, ROS formation and DNA damage are critical factors in the cellular toxicity of 7-hydroxy-β-lapachone.
authors.affiliation: BioLab, Instituto Universitario de Bio-Orgánica Antonio González, Universidad de La Laguna, 38206 La Laguna, Spain.
authors.forename: Carla
authors.initials: C
authors.lastname: Ríos-Luci
authors.forename: Evelyn L
authors.initials: EL
authors.lastname: Bonifazi
authors.forename: Leticia G
authors.initials: LG
authors.lastname: León
authors.forename: Juan C
authors.initials: JC
authors.lastname: Montero
authors.forename: Gerardo
authors.initials: G
authors.lastname: Burton
authors.forename: Atanasio
authors.initials: A
authors.lastname: Pandiella
authors.forename: Rosana I
authors.initials: RI
authors.lastname: Misico
authors.forename: José M
authors.initials: JM
authors.lastname: Padrón
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D026942:DNA Topoisomerases / Q000378:metabolism; D006801:Humans; D009285:Naphthoquinones / Q000737:chemistry* / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D059003:Topoisomerase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D009285:Naphthoquinones; D017382:Reactive Oxygen Species; D059003:Topoisomerase Inhibitors; C014638:beta-lapachone; D026942:DNA Topoisomerases; C415043:alpha-lapachone