title: Evaluation of apoptotic effect of cyclic imide derivatives on murine B16F10 melanoma cells.
abstract: Cyclic imides are a large class of compounds obtained by organic synthesis including several sub-classes (succinimides maleimide, glutarimide, phthalimides naphtalimides, and its derivatives). Recently, some cyclic imide derivatives have shown important results as potential antitumor agents, as a Mitonafide and Amonafide. Based on this fact, we have studied antitumoral properties of nine cyclic imide derivatives, four of which are unpublished compounds, against Murine Melanoma Cells (B16F10). Initially, the MTT assay was used to select the compound with the best cytotoxic potential. After this selection, the compound 2-benzyl-1H-benzo[de]isoquinoline-1,3(2H)-dione (4), which showed the best cytotoxic effects, was evaluated by flow cytometry, and a significant increase was observed in the proportion of cells in the subG0/G1, S and G2/M phases accompanied by a significant decrease in the G0/G1 phases. Then the mechanism involved on the death route (necrosis or apoptosis) was evaluated the by bromide and acridine orange method and by an Annexin V-FITC Apoptosis Detection kit. These results confirm that the percentage of B16F10 cells observed in the sub G0/G1 phase were undergoing apoptosis. The biological effects observed in the current study for the cyclic imide derivatives suggested promising applications, especially for the prototype compound 4.
authors.affiliation: Departamento de Análises Clínicas, Universidade Federal de Santa Catarina, UFSC, 89, Campus Trindade, CEP 88040-900, Florianópolis, Santa Catarina, Brazil.
authors.forename: Karina Elisa
authors.initials: KE
authors.lastname: Machado
authors.forename: Kely Navakoski de
authors.initials: KN
authors.lastname: Oliveira
authors.forename: Lorena
authors.initials: L
authors.lastname: Santos-Bubniak
authors.forename: Marley Aparecida
authors.initials: MA
authors.lastname: Licínio
authors.forename: Ricardo José
authors.initials: RJ
authors.lastname: Nunes
authors.forename: Maria Cláudia
authors.initials: MC
authors.lastname: Santos-Silva
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D020128:Inhibitory Concentration 50; D007546:Isoquinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D053644:Naphthalimides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013055:Spectrophotometry, Infrared
chemical_list: D000970:Antineoplastic Agents; D007546:Isoquinolines; D053644:Naphthalimides