title: Photocytotoxicity of a 5-nitrofuran-ethenyl-quinoline antiseptic (Quinifuryl) to P388 mouse leukemia cells.
abstract: Quinifuryl (MW 449.52), 2-(5'-nitro-2'-furanyl)ethenyl-4-[N-[4'-(N,N-diethylamino)-1'-methylbutyl]carbamoyl] quinoline, is a water soluble representative of a family of 5-nitrofuran-ethenyl-quinoline drugs which has been shown to be highly toxic to various lines of transformed cells in the dark. In the present study, the toxicity of Quinifuryl to P388 mouse leukemia cells was compared in the dark and under illumination with visible light (390-500 nm). Illumination of water solutions of Quinifuryl (at concentrations ranging from 0.09 to 9.0 microg/ml) in the presence of P388 cells resulted in its photodecomposition and was accompanied by elevated cytotoxicity. A significant capacity to kill P388 cells was detected at a drug concentration as low as 0.09 microg/ml. The toxic effect detected at this drug concentration under illumination exceeded the effect observed in the dark by more than three times. Moreover, the general toxic effect of Quinifuryl, which included cell proliferation arrest, was nearly 100%. Both dose- and time-dependent toxic effects were measured under illumination. The LC50 value of Quinifuryl during incubation with P388 cells was approximately 0.45 microg/ml under illumination for 60 min and >12 microg/ml in the dark. We have demonstrated that the final products of the Quinifuryl photolysis are not toxic, which means that the short-lived intermediates of Quinifuryl photodecomposition are responsible for the phototoxicity of this compound. The data obtained in the present study are the first to indicate photocytotoxicity of a nitroheterocyclic compound and demonstrate the possibility of its application as a photosensitizer drug for photochemotherapy.
authors.affiliation: Departamento de Física e Matemática, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: N A
authors.initials: NA
authors.lastname: Daghastanli
authors.forename: I A
authors.initials: IA
authors.lastname: Degterev
authors.forename: A C
authors.initials: AC
authors.lastname: Tedesco
authors.forename: I E
authors.initials: IE
authors.lastname: Borissevitch
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003624:Darkness; D004353:Drug Evaluation, Preclinical; D007941:Leukemia P388 / Q000188:drug therapy* / Q000473:pathology; D008029:Lighting; D051379:Mice; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000627:therapeutic use*; D011804:Quinolines / Q000737:chemistry / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D017319:Photosensitizing Agents; D011804:Quinolines; C099760:quinifuryl