Selenoxanthones via directed metalations in 2-arylselenobenzamide derivatives.

The reaction of N, N-diethyl 4-(N', N'-dimethylamino)-2-phenylselenobenzamide (7a), N, N-diethyl 4-methoxy-2-phenylselenobenzamide (7b), N, N-diethyl 4-(N', N'-dimethylamino)-2-[(3-(N, N-dimethylamino)phenylseleno]benzamide (7c), and N, N-diethyl 4-methoxy-2-(3-methoxyphenylseleno)-benzamide (7d) with excess lithium diisopropylamide (LDA) gave 2-N, N-(dimethylamino)-9H-selenoxanthone (9a), 2-methoxy-9H-selenoxanthone (9b), 2,7-bis-N, N-(dimethylamino)-9H-selenoxanthone (9c), and 2,5-dimethoxy-9H-selenoxanthone (9d) in 70%, 59%, 23%, and 90% isolated yields, respectively. N, N-Diethyl 2-phenylselenobenzamide (2-Se) gave no reaction with LDA, t-BuLi, MeLi, or lithium 2,2,6,6-tetramethylpiperidide as base. Electron donation from the 4-substituent of benzamide derivatives 7a-7d may increase the directing ability of the carbonyl oxygen to metalate the 2-position of the arylseleno group.

In vitro photodynamic properties of chalcogenopyrylium analogues of the thiopyrylium antitumor agent AA1.

Several series of chalcogenopyrylium dyes were prepared with one or two 4-anilino substituents at the 2- and 6-positions and with phenyl, 4-N,N-dimethylanilino, or 4-(N-morphilino)phenyl substituents at 2- and/or 4-positions. The dye series are all related in structure to AA1, a thiopyrylium dye that targets mitochondria. The chalcogenopyrylium nuclei included sulfur, selenium, and tellurium at the 1-position. Key intermediates in the dye synthesis were the corresponding Delta-4H-chalcogenopyran-4-ones. All of the dyes of this study were evaluated for dark and phototoxicity toward Colo-26 cells in vitro. There was no correlation of dark toxicity with either the reduction potential of the chalcogenopyrylium dye or the n-octanol/water partition coefficient, log P. Several of the dyes of this study (thiopyrylium dyes 1-S and 13-S, selenopyrylium dyes 1-Se, 2-Se, 3-Se, 4-Se, 13-Se, 14-Se, and 27-Se, and telluropyrylium dye 13-Te) showed added phototoxicity upon irradiation. Dyes with the highest therapeutic ratio as measured by dark toxicity/phototoxicity (15 J cm(-2) of 360-800-nm light) had values of log P of 1.0-1.2. Studies of cytochrome c oxidase activity in whole R3230AC cells suggested that dyes 1-S and 3-Se, with values of log P of 2.2 and 1.7, respectively, were localized in the mitochondria. Cytocrome c oxidase activity in whole cells was inhibited by 1-S and 3-Se in the dark. Chalcogenopyrylium dyes 2-Se, 4-Se, 13-Te, and 14-Se inhibited whole-cell cytochrome c oxidase activity only following irradiation, which suggests that these dyes relocalized to mitochondria following irradiation.