title: Synthesis, crystal structure and effect of indeno[1,2-b]indole derivatives on prostate cancer in vitro. Potential effect against MMP-9.
abstract: A highly regiospecific synthesis of a series of indenoindoles is reported, together with X-ray studies and their activity against human prostate cancer cells PC-3 and LNCaP in vitro. The most effective compound 7,7-dimethyl-5-[(3,4-dichlorophenyl)]-(4bRS,9bRS)-dihydroxy-4b,5,6,7,8,9bhexahydro-indeno[1,2-b]indole-9,10-dione 7q reduced the viability in both cell lines in a time and dose-dependent manner. Inhibitory effects were also observed on the adhesion, migration, and invasion of the prostate cancer cells as well as on clonogenic possibly by inhibition of MMP-9 activity. Molecular docking of 7q and 6k into MMP-9 human active site was also performed to determine the probable binding mode.
authors.affiliation: Laboratorio de Síntesis Orgánica, Unidad de Bioquímica, Facultad de Farmacia, Universidad Central de Venezuela, Apartado 47206, Los Chaguaramos, 1041-A Caracas, Venezuela.
authors.forename: Gricela
authors.initials: G
authors.lastname: Lobo
authors.affiliation: Laboratorio de Síntesis Orgánica, Unidad de Bioquímica, Facultad de Farmacia, Universidad Central de Venezuela, Apartado 47206, Los Chaguaramos, 1041-A Caracas, Venezuela.
authors.forename: Melina
authors.initials: M
authors.lastname: Monasterios
authors.affiliation: Laboratorio de Síntesis Orgánica, Unidad de Bioquímica, Facultad de Farmacia, Universidad Central de Venezuela, Apartado 47206, Los Chaguaramos, 1041-A Caracas, Venezuela.
authors.forename: Juan
authors.initials: J
authors.lastname: Rodrigues
authors.affiliation: Laboratorio de Síntesis Orgánica, Unidad de Bioquímica, Facultad de Farmacia, Universidad Central de Venezuela, Apartado 47206, Los Chaguaramos, 1041-A Caracas, Venezuela.
authors.forename: Neira
authors.initials: N
authors.lastname: Gamboa
authors.affiliation: Unidad de Estructura Molecular, Fundación Instituto de Estudios Avanzados (IDEA), Apartado 17606, Caracas 1015-A, Venezuela.
authors.forename: Mario V
authors.initials: MV
authors.lastname: Capparelli
authors.affiliation: Servicio de Difracción de Rayos X, Universidad Autónoma de Barcelona, 08193 Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Martínez-Cuevas
authors.affiliation: Department of Urology, University Hospital Charité, Campus Mitte, Schumannstrasse 20/21, 10117 Berlin, Germany; Berlin Institute for Urologic Research, Schumannstrasse 22/21, 10117 Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Lein
authors.affiliation: Department of Urology, University Hospital Charité, Campus Mitte, Schumannstrasse 20/21, 10117 Berlin, Germany; Berlin Institute for Urologic Research, Schumannstrasse 22/21, 10117 Berlin, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Jung
authors.affiliation: Department of Urology, University Hospital Charité, Campus Mitte, Schumannstrasse 20/21, 10117 Berlin, Germany; Department of Experimental Medicine (FEM), University Hospital Charité, Campus Mitte, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Abramjuk
authors.affiliation: Laboratorio de Síntesis Orgánica, Unidad de Bioquímica, Facultad de Farmacia, Universidad Central de Venezuela, Apartado 47206, Los Chaguaramos, 1041-A Caracas, Venezuela. Electronic address: jaime.charris@ucv.ve.
authors.forename: Jaime
authors.initials: J
authors.lastname: Charris
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007192:Indenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D007192:Indenes; D007211:Indoles; D061965:Matrix Metalloproteinase Inhibitors; C000606774:indeno(1,2-b)indole; D020780:Matrix Metalloproteinase 9
keywords: Cancer; Crystal; Indeno; MMP-9; Prostate; Regiospecif