title: QSAR on antiproliferative naphthoquinones based on a conformation-independent approach.
abstract: The antiproliferative activities of a series of 36 naphthoquinone derivatives were subjected to a Quantitative Structure-Activity Relationships (QSAR) study. For this purpose a panel of four human cancer cell lines was used, namely HBL-100 (breast), HeLa (cervix), SW-1573 (non-small cell lung) and WiDr (colon). A conformation-independent representation of the chemical structure was established in order to avoid leading with the scarce experimental information on X-ray crystal structure of the drug interaction. The 1179 theoretical descriptors derived with E-Dragon and Recon software were simultaneously analyzed through linear regression models based on the Replacement Method variable subset selection technique. The established models were validated and tested through the use of external test sets of compounds, the Leave-One-Out Cross Validation method, Y-Randomization and Applicability Domain analysis.
authors.affiliation: Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas INIFTA (UNLP, CCT La Plata-CONICET), Diag. 113 y 64, C.C. 16, Sucursal 4, 1900 La Plata, Argentina. Electronic address: pabloducho@gmail.com.
authors.forename: Pablo R
authors.initials: PR
authors.lastname: Duchowicz
authors.affiliation: Cátedra de Química Orgánica, Facultad de Ciencias Agrarias y Forestales, Universidad Nacional de La Plata (UNLP), 60 y 119, B1904AAN La Plata, Argentina.
authors.forename: Daniel O
authors.initials: DO
authors.lastname: Bennardi
authors.affiliation: Departamento de Química, Facultad de Ciencias Exactas y Naturales, Universidad de Belgrano, Villanueva 1324, C1426BMJ Ciudad de Buenos Aires, Argentina.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Bacelo
authors.affiliation: Departamento de Química Orgánica y UMYMFOR (CONICET-UBA), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2, Ciudad Universitaria, C1428EGA Ciudad de Buenos Aires, Argentina.
authors.forename: Evelyn L
authors.initials: EL
authors.lastname: Bonifazi
authors.affiliation: BioLab, Instituto Universitario de Bio-Orgánica "Antonio González" (IUBO-AG), Centro de Investigaciones Biomédicas de Canarias (CIBICAN), Universidad de La Laguna, C/Astrofísico Francisco Sánchez 2, 38206 La Laguna, Spain.
authors.forename: Carla
authors.initials: C
authors.lastname: Rios-Luci
authors.affiliation: BioLab, Instituto Universitario de Bio-Orgánica "Antonio González" (IUBO-AG), Centro de Investigaciones Biomédicas de Canarias (CIBICAN), Universidad de La Laguna, C/Astrofísico Francisco Sánchez 2, 38206 La Laguna, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Padrón
authors.affiliation: Departamento de Química Orgánica y UMYMFOR (CONICET-UBA), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2, Ciudad Universitaria, C1428EGA Ciudad de Buenos Aires, Argentina.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Burton
authors.affiliation: Departamento de Química Orgánica y UMYMFOR (CONICET-UBA), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2, Ciudad Universitaria, C1428EGA Ciudad de Buenos Aires, Argentina. Electronic address: misicori@qo.fcen.uba.ar.
authors.forename: Rosana I
authors.initials: RI
authors.lastname: Misico
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D008968:Molecular Conformation; D009285:Naphthoquinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D009285:Naphthoquinones
keywords: Cancer; Molecular descriptors; Multivariable linear regression; Naphthoquinone derivative; QSAR theory