Photocytotoxicity of the fluorescent nonsteroidal androgen receptor ligand TDPQ.
Photocytotoxicity of the fluorescent nonsteroidal androgen receptor ligand TDPQ.
复制标题
荧光非甾体雄激素受体配体 TDPQ 的光细胞毒性。
DOI：
10.1111/j.1751-1097.2009.00575.x
复制
发表时间：
2009
影响因子：
3.3
通讯作者：
Schrader,WilliamT
中科院分区：
文献类型：
--
作者：
Bilski,PiotrJ;Risek,Boris;Chignell,ColinF;Schrader,WilliamT
1,2,3,4-四氢-2,2-二甲基-6-(三氟甲基)-8-吡啶并[5,6-g]喹啉 (TDPQ) 是一种选择性非甾体雄激素受体 (AR) 配体，是一种荧光化合物。我们与结构前体喹诺酮 151 (C151) 及其外消旋结构异构体 4-乙基-1,2,3,4-四氢-6-(三氟甲基)-8-吡啶基[5,6-g]喹啉 (ETPQ) 进行了比较，对其光谱特性进行了表征。 TDPQ 或 ETPQ 在 CH3CN 中的最大吸收波长为 400 nm，而 C151 的最大吸收波长为 350 nm。 CH3CN 中的荧光寿命 (τ) 和量子产率 (phif) 是荧光染料的典型特征：TDPQ (4.2 ns, 0.8) 和 ETPQ (4.6 ns, 0.76)。 C151 的 τ 和 phif 分别较低，分别为 0.2 ns 和 0.02。 TDPQ 可以作为（亚）微摩尔浓度的荧光标记。我们使用共聚焦显微镜检测了人类乳腺肿瘤细胞中的 TDPQ 荧光。虽然化合物的荧光最大值对溶剂不敏感，但无论是否存在白蛋白或 DNA，ETPQ 的 Φf 在水溶液中都会降低。 TDPQ 的 ψf 受到的影响较小。 CH3CN 中 TDPQ 和 ETPQ 的单线态氧 (1O2) 光敏化 (ψso) 量子产率约为 7%，足以诱导光细胞毒性。 TDPQ 在 AR 阳性 MDA-MB-453 乳腺癌细胞中具有光细胞毒性，但在 AR 阴性 MDA-MB-231 细胞中没有光细胞毒性。 AR 选择性与光细胞毒性的结合使 TDPQ 成为光动力治疗期间选择性靶向 AR 阳性细胞的有希望的候选者。
1,2,3,4‐tetrahydro‐2,2‐dimethyl‐6‐(trifluoromethyl)‐8‐pyridono[5,6‐g]quinoline (TDPQ), a selective nonsteroidal androgen receptor (AR) ligand, is a fluorescent compound. We characterized its spectral properties in comparison with the structural precursor carbostyril 151 (C151) and with its racemic structural isomer 4‐ethyl‐1,2,3,4‐tetrahydro‐6‐(trifluoromethyl)‐8‐pyridino[5,6‐g]quinoline (ETPQ). The absorption maximum in CH3CN of either TDPQ or ETPQ is 400 nm whereas that of C151 is 350 nm. The fluorescence lifetimes (τ) and quantum yields (ϕf) in CH3CN are typical of fluorescent dyes: TDPQ (4.2 ns, 0.8) and ETPQ (4.6 ns, 0.76). C151 showed lowerτandϕfof 0.2 ns and 0.02, respectively. TDPQ can function as a fluorescent label at (sub)micromolar concentrations. We detected TDPQ fluorescence in human breast tumor cells using confocal microscopy. While the fluorescence maxima of the compounds were solvent insensitive, theϕffor ETPQ decreased in aqueous solutions regardless of the presence of albumin or DNA. Theϕfof TDPQ was less affected. The quantum yield of singlet oxygen (1O2) photosensitization (ϕso) by TDPQ and ETPQ was about 7% in CH3CN, sufficient to induce photocytotoxicity. TDPQ was photocytotoxic in AR‐positive MDA‐MB‐453 breast cancer cells but not in AR‐negative MDA‐MB‐231 cells. The combination of AR selectivity with photocytotoxicity makes TDPQ a promising candidate for selective targeting of AR‐positive cells during photodynamic therapy.