title: Ester of Quinoxaline-7-carboxylate 1,4-di-N-oxide as Apoptosis Inductors in K-562 Cell Line: An in vitro, QSAR and DFT Study.
abstract: BACKGROUND
  Quinoxalines have shown a wide variety of biological activities including as antitumor agents. The aims of this study were to evaluate the activity of quinoxaline 1,4-di-N-oxide derivatives on K562 cells, the establishment of the mechanism of induced cell death, and the construction of predictive QSAR models.
  
  
  METHODS
  Sixteen esters of quinoxaline-7-carboxylate 1,4-di-N-oxide were evaluated for antitumor activity on K562 chronic myelogenous leukemia cells and their IC50 values were determined. The mechanism of induced cell death by the most active molecule was assessed by flow cytometry and an in silico study was conducted to optimize and calculate theoretical descriptors of all quinoxaline 1,4-di-N-oxide derivatives. QSAR and QPAR models were created using genetic algorithms.
  
  
  CONCLUSIONS
  Our results show that compounds C5, C7, C10, C12 and C15 had the lowest IC50 of the series. C15 was the most active compound (IC50= 3.02 μg/mL), inducing caspase-dependent apoptotic cell death via the intrinsic pathway. QSAR and QPAR studies are discussed.
authors.affiliation: Centro de Biotecnología Genómica, Instituto Politécnico Nacional, Reynosa, 88710, Mexico.
authors.forename: Gildardo
authors.initials: G
authors.lastname: Rivera
authors.affiliation: Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Carpio y Plan de Ayala, s/n, 11340, D.F., Mexico.
authors.forename: Sergio
authors.initials: S
authors.lastname: Andrade-Ochoa
authors.affiliation: Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Carpio y Plan de Ayala, s/n, 11340, D.F., Mexico.
authors.forename: Manolo S Ortega
authors.initials: MSO
authors.lastname: Romero
authors.affiliation: Unidad Académica Multidisciplinaria Reynosa-Rodhe, Universidad Autónoma de Tamaulipas, Reynosa, 88779, Mexico.
authors.forename: Isidro
authors.initials: I
authors.lastname: Palos
authors.affiliation: Neglected Diseases Section, Drug R&D Unit, Center for Applied Pharmacobiology Research, University of Navarra, C/Irunlarrea 1, 31008 Pamplona. Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Monge
authors.affiliation: Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Carpio y Plan de Ayala, s/n, 11340, D.F., Mexico.
authors.forename: Luvia Enid
authors.initials: LE
authors.lastname: Sanchez-Torres
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D003497:Cyclic N-Oxides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020014:K562 Cells; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D011789:Quantum Theory; D011810:Quinoxalines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D003497:Cyclic N-Oxides; D011810:Quinoxalines
keywords: 4-di-N-oxide; DFT; QSAR; Quinoxaline 1; anti-cancer; apoptosis