You Youngjae, Gibson Scott L, Detty Michael R
Institute for Lasers, Photonics, and Biophotonics, Department of Chemistry, University at Buffalo, The State University of New York, Buffalo, NY 14260, USA.
Bioorg Med Chem. 2005 Nov 1;13(21):5968-80. doi: 10.1016/j.bmc.2005.07.006.
21,23-Dithiaporphyrins 2-11 were prepared as analogues of 5,20-diphenyl-10,15-bis(4-carboxylatomethoxy)phenyl-21,23-dithiaporphyrin 1 to examine the impact of electronic properties at the 5- and 20-meso-positions. The effects of the electronic properties at the meso-rings were not significant with respect to absorption spectra, quantum yields for the generation of singlet oxygen and for fluorescence. While some differences were noted in the n-octanol/pH 7.4 buffer partition coefficient, log D(7.4), among the compounds, log D(7.4) did not critically influence the cellular uptake or phototoxicity. None of the dithiaporphyrins 1-11 displayed dark toxicity at concentrations up to 1 x 10(-5) M. Once irradiated with 5 J cm(-2) of 350-750 nm light, five porphyrins 2, 3, 5, 6, and 8 killed over 80% of R3230AC rat mammary adenocarcinoma cells at 5 x 10(-7) M photosensitizer. Among these five, compound 3 bearing 5-phenyl and 20-(4-fluorophenyl) substituents was the most potent photosensitizer toward R3230AC cells showing 67% cell kill at 1 x 10(-7) M 3. Bulky substituents at the 5- and 20-positions gave photosensitizers with minimal phototoxicity.
制备了21,23 - 二硫杂卟啉2 - 11作为5,20 - 二苯基 - 10,15 - 双(4 - 羧基甲氧基)苯基 - 21,23 - 二硫杂卟啉1的类似物，以研究5 - 和20 - 中位位置电子性质的影响。中位环上电子性质对吸收光谱、单线态氧生成的量子产率和荧光量子产率的影响并不显著。虽然在化合物之间观察到正辛醇/pH 7.4缓冲液分配系数log D(7.4)存在一些差异，但log D(7.4)对细胞摄取或光毒性没有关键影响。二硫杂卟啉1 - 11在浓度高达1×10⁻⁵ M时均未表现出暗毒性。一旦用5 J cm⁻²的350 - 750 nm光照射，五种卟啉2、3、5、6和8在5×10⁻⁷ M光敏剂浓度下杀死了超过80%的R3230AC大鼠乳腺腺癌细胞。在这五种中，带有5 - 苯基和20 - (4 - 氟苯基)取代基的化合物3是对R3230AC细胞最有效的光敏剂，在1×10⁻⁷ M的3浓度下显示出67%的细胞杀伤率。5 - 和20 - 位上的庞大取代基产生的光敏剂光毒性最小。
