title: Multivariate SAR and QSAR of cucurbitacin derivatives as cytotoxic compounds in a human lung adenocarcinoma cell line.
abstract: This article describes structure-activity relationship (SAR/QSAR) studies on the cytotoxic activity in a human lung adenocarcinoma cell line (A549) of 43 cucurbitacin derivatives. Modeling was performed using the methods partial least squares with discriminant analysis (PLS-DA) and PLS. For both studies, the variables were selected using the ordered predictor selection (OPS) algorithm. The SAR study demonstrated that the presence or absence of cytotoxic activity of the cucurbitacins could be described using information derived from their chemical structures. The QSAR study displayed suitable internal and external predictivity, and the selected descriptors indicated that the observed activity might be related to electrophilic attack on cellular structures or genetic material. This study provides improves the understanding of the cytotoxic activity of cucurbitacins and could be used to propose new cytotoxic agents.
authors.affiliation: Department of Pharmacy, Federal University of Juiz de Fora (UFJF), Campus Governador Valadares, MG, Brazil.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Lang
authors.affiliation: Department of Pharmaceutical Sciences, Federal University of Santa Catarina (UFSC), Florianópolis, SC, Brazil.
authors.forename: Izabella T
authors.initials: IT
authors.lastname: Silva
authors.affiliation: Department of Pharmaceutical Sciences, Federal University of Santa Catarina (UFSC), Florianópolis, SC, Brazil.
authors.forename: Vanessa R
authors.initials: VR
authors.lastname: Machado
authors.affiliation: Department of Pharmaceutical Sciences, Federal University of Santa Catarina (UFSC), Florianópolis, SC, Brazil.
authors.forename: Lara A
authors.initials: LA
authors.lastname: Zimmermann
authors.affiliation: Department of Chemistry, Federal University of Santa Catarina (UFSC), Florianópolis, SC, Brazil.
authors.forename: Miguel S B
authors.initials: MS
authors.lastname: Caro
authors.affiliation: Department of Pharmaceutical Sciences, Federal University of Santa Catarina (UFSC), Florianópolis, SC, Brazil.
authors.forename: Cláudia M O
authors.initials: CM
authors.lastname: Simões
authors.affiliation: Department of Pharmaceutical Sciences, Federal University of Santa Catarina (UFSC), Florianópolis, SC, Brazil.
authors.forename: Eloir P
authors.initials: EP
authors.lastname: Schenkel
authors.affiliation: UMYMFOR-CONICET, Department of Organic Chemistry, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Durán
authors.affiliation: Department of Pharmaceutical Sciences, Federal University of Santa Catarina (UFSC), Florianópolis, SC, Brazil.
authors.forename: Lílian S C
authors.initials: LS
authors.lastname: Bernardes
authors.affiliation: Theoretical Medicinal and Environmental Chemistry Laboratory (LQMAT), Department of Pharmacy, Western Paraná State University (Unioeste), Cascavel, PR, Brazil. Electronic address: eduardo.b.de.melo@gmail.com.
authors.forename: Eduardo B
authors.initials: EB
authors.lastname: de Melo
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D054728:Cucurbitacins / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D015999:Multivariate Analysis; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D054728:Cucurbitacins
keywords: Cucurbitacins; Lung cancer; OPS; PLS; PLS-DA; QSAR