Bilski Piotr J, Risek Boris, Chignell Colin F, Schrader William T
Laboratory of Pharmacology, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA.
Photochem Photobiol. 2009 Sep-Oct;85(5):1225-32. doi: 10.1111/j.1751-1097.2009.00575.x. Epub 2009 May 28.
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 (tau) and quantum yields (phif) in CH3CN are typical of fluorescent dyes: TDPQ (4.2 ns, 0.8) and ETPQ (4.6 ns, 0.76). C151 showed lower tau and phif of 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, the phif for ETPQ decreased in aqueous solutions regardless of the presence of albumin or DNA. The phif of TDPQ was less affected. The quantum yield of singlet oxygen (1O2) photosensitization (phiso) 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.
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。我们将其光谱特性与结构前体卡巴司替丁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-吡啶并[5,6-g]喹啉（ETPQ）进行了比较。TDPQ或ETPQ在乙腈中的最大吸收波长为400nm，而C151的最大吸收波长为350nm。在乙腈中，荧光寿命（τ）和量子产率（φf）是典型的荧光染料特性：TDPQ（4.2ns，0.8）和ETPQ（4.6ns，0.76）。C151的τ和φf较低，分别为0.2ns和0.02。TDPQ在（亚）微摩尔浓度下可作为荧光标记物。我们使用共聚焦显微镜在人乳腺肿瘤细胞中检测到了TDPQ荧光。虽然这些化合物的荧光最大值对溶剂不敏感，但无论有无白蛋白或DNA，ETPQ在水溶液中的φf都会降低。TDPQ的φf受影响较小。TDPQ和ETPQ在乙腈中对单线态氧（1O2）的光敏化量子产率（φiso）约为7%，足以诱导光细胞毒性。TDPQ对AR阳性的MDA-MB-453乳腺癌细胞具有光细胞毒性，但对AR阴性的MDA-MB-231细胞没有光细胞毒性。AR选择性与光细胞毒性的结合使TDPQ成为光动力疗法中选择性靶向AR阳性细胞的有前景的候选物。
