Comparison of the dark and light-induced toxicity of thio and seleno analogues of the thiopyrylium dye AA1.
2,6-Bis(4-anilino)-4-(4-N,N-dimethylanilino)thiopyrylium chloride (AA1) and -selenopyrylium chloride (AA1-Se) and 2,6-bis(4-anilino)-4-(4-N-morpholinophenyl)thiopyrylium chloride (1) and -selenopyrylium chloride (2) were prepared via the addition of 4-N,N-dimethylanilino magnesium bromide and 4-N-morpholinophenyl magnesium bromide to chalcogenopyranones 3 followed by treatment with HCl gas then water. Cellular uptake of these dyes varied from 12+/-3fmol/cell for AA1 to 150+/-40 fmol/cell for AA1-Se. upon exposure to 5 x 10(-5) M solutions of the dyes for 3 h. Exposure of cell cultures to 1.8 J/cm2) of 360-750-nm light following incubation with 1 x 10(-6) M of either AA1, 1, or 2 for 24h resulted in no significant additional phototoxicity while AA1-Se showed a significant (p < 0.05) reduction in cell viability from 81% to 46%. Thiopyrylium dyes AA1 and 1 showed significant dark toxicity relative to selenopyrylium dyes AA1-Se and 2, respectively. AA1 was the only one of the four dyes to show inhibition of whole-cell mitochondrial cytochrome c oxidase activity in the dark. Irradiation of whole cells or mitochondrial suspensions treated with AA1, AA1-Se, or 2 gave inhibition of mitochondrial cytochrome c oxidase activity. Studies of JC-1-efflux indicated that all four cationic dyes accelerated the loss of JC-1 from the mitochondria, which suggests that all four dyes target the mitochondria.
Detty
Michael R
MR
Department of Chemistry, University at Buffalo, The State University of New York, Buffalo, NY 14260, USA. mdetty@buffalo.edu
Gibson
Scott L
SL
Hilf
Russell
R
D000814:Aniline Compounds / Q000737:chemistry* / Q000633:toxicity*; D000818:Animals; D001562:Benzimidazoles / Q000032:analysis; D002232:Carbocyanines / Q000032:analysis; D045744:Cell Line, Tumor; D002470:Cell Survival; D004396:Coloring Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity*; D003624:Darkness; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors; D008027:Light; D008928:Mitochondria / Q000187:drug effects; D015394:Molecular Structure; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity*; D051381:Rats; D012643:Selenium / Q000737:chemistry; D018036:Selenium Compounds / Q000737:chemistry / Q000633:toxicity; D013876:Thiophenes / Q000737:chemistry* / Q000633:toxicity*
C493772:2,6-Bis(4-anilino)-4-(4-N,N-dimethylanilino)thiopyrylium chloride; C493774:2,6-bis(4-anilino)-4-(4-N-morpholinophenyl)thiopyrylium chloride; D000814:Aniline Compounds; D001562:Benzimidazoles; D002232:Carbocyanines; D004396:Coloring Agents; D017319:Photosensitizing Agents; D018036:Selenium Compounds; D013876:Thiophenes; C493773:selenopyrylium chloride; C086431:2,6-bis(4-aminophenyl)-4-(4-(dimethylamino)phenyl)thiopyrylium; C068624:5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine; D003576:Electron Transport Complex IV; D012643:Selenium