title: Synthesis and anticancer activity evaluation of new 2-alkylcarbonyl and 2-benzoyl-3-trifluoromethyl-quinoxaline 1,4-di-N-oxide derivatives.
abstract: As a continuation of our research in quinoxaline 1,4-di-N-oxide and with the aim of obtaining new anticancer agents, which can improve the current chemotherapeutic treatments, new series of 2-alkylcarbonyl and 2-benzoyl-3-trifluoromethylquinoxaline 1,4-di-N-oxide derivatives have been synthesized and evaluated for in vitro antitumor activity against a 3-cell line panel, consisting of MCF7 (breast), NCI-H460 (lung), and SF-268 (CNS). These active compounds were then evaluated in the full panel of 60 human tumor cell lines derived from nine cancer cell types. The results have shown that, in general, anticancer activity depends on the substituents in the carbonyl group, improving in the order: ethyl<isopropyl<tert-butyl<phenyl-ones. Among these, the compounds 4c, 6e, their difluorinated analogs (4g and 6g), and 5c were the most active, with mean GI(50) values of 1.02, 0.42, 0.52, 0.15, and 0.49microM, respectively. All of them were also found to inhibit the growth of the all of the Leukemia cell lines studied (with 75% of the GI(50) values less than 0.15microM) and therefore, were selected for further evaluation for the in vivo hollow fiber assays.
authors.affiliation: Unidad en Investigación y Desarrollo de Medicamentos, Centro de Investigación en Farmacobiología Aplicada, Universidad de Navarra, c/ Irunlarrea s/n, 31080 Pamplona, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: Zarranz
authors.forename: Andrés
authors.initials: A
authors.lastname: Jaso
authors.forename: Ignacio
authors.initials: I
authors.lastname: Aldana
authors.forename: Antonio
authors.initials: A
authors.lastname: Monge
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D011810:Quinoxalines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D011810:Quinoxalines; C003282:quindoxin