2,4,6-triarylchalcogenopyrylium dyes related in structure to the antitumor agent AA1 as in vitro sensitizers for the photodynamic therapy of cancer.
2,4,6-triarylchalcogenopyrylium dyes related in structure to the antitumor agent AA1 as in vitro sensitizers for the photodynamic therapy of cancer.
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2,4,6-三芳基硫属吡咯鎓染料在结构上与抗肿瘤剂 AA1 相关，作为癌症光动力疗法的体外敏化剂。
DOI：
10.1021/jm990134r
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发表时间：
1999
影响因子：
7.3
通讯作者：
Detty,MR
中科院分区：
文献类型：
--
作者：
Leonard,KA;Nelen,MI;Anderson,LT;Gibson,SL;Hilf,R;Detty,MR
阳离子硫属吡喃鎓染料2−4由4-(二甲基氨基)苯乙炔(7)分六步合成，在甲醇中的最大吸收分别为594、631和672 nm，并产生量子产率[Φ(1O2)]分别为0.020、0.064和0.037的单线态氧。染料 2−4 比之前评估为光动力疗法敏化剂的其他硫属吡咯鎓染料在水解上更稳定。在 10 μM 终浓度下，所有染料 2−4 在用 10 μM 染料处理的肿瘤线粒体悬浮液照射期间均抑制细胞色素氧化酶。在低氧环境和存在咪唑（单线态氧陷阱）的情况下，酶抑制程度减弱。终浓度为 30 U 的超氧化物歧化酶不会改变染料 2−4 对线粒体细胞色素氧化酶的光敏抑制作用。这些数据表明单线态氧可能在线粒体细胞色素氧化酶的光敏抑制中起主要作用。在染料 2−4 存在的情况下，对 R3230AC 大鼠乳腺癌细胞进行辐照，导致细胞活力显着丧失，其中硫代吡啶鎓染料 2 显示出最大的光毒性。初步的体内急性毒性研究表明，在 10 mg/kg 浓度下，三种染料均未表现出明显的毒性。
Cationic chalcogenopyrylium dyes2−4were synthesized in six steps from 4-(dimethylamino)phenylethyne (7), have absorption maxima in methanol of 594, 631, and 672 nm, respectively, and generate singlet oxygen with quantum yields [Φ(1O2)] of 0.020, 0.064, and 0.037, respectively. Dyes2−4are hydrolytically more stable than other chalcogenopyrylium dyes evaluated previously as sensitizers for photodynamic therapy. At 10 μM final concentration, all dyes2−4inhibited cytochromecoxidase during irradiation of tumor mitochondrial suspensions treated with 10 μM dye. The degree of enzyme inhibition was abated in a reduced oxygen environment and in the presence of imidazole, a singlet oxygen trap. Superoxide dismutase, at a final concentration of 30 U, did not alter the photosensitized inhibition of mitochondrial cytochromecoxidase by dyes2−4. These data suggest that singlet oxygen may play a major role in the photosensitized inhibition of mitochondrial cytochromecoxidase. Irradiation of R3230AC rat mammary adenocarcinoma cells in the presence of dyes2−4caused a significant loss in cell viability with thiopyrylium dye2displaying the greatest phototoxicity. Initial acute toxicity studies in vivo demonstrate that, at 10 mg/kg, none of the three dyes displayed overt toxicity.