Premium
Photocytotoxicity of the Fluorescent Nonsteroidal Androgen Receptor Ligand TDPQ †
Author(s) -
Bilski Piotr J.,
Risek Boris,
Chignell Colin F.,
Schrader William T.
Publication year - 2009
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.2009.00575.x
Subject(s) - chemistry , fluorescence , quinoline , quantum yield , singlet oxygen , ligand (biochemistry) , trifluoromethyl , androgen receptor , selectivity , photodynamic therapy , photochemistry , receptor , oxygen , alkyl , cancer , organic chemistry , biochemistry , biology , physics , prostate cancer , quantum mechanics , genetics , catalysis
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 CH 3 CN of either TDPQ or ETPQ is 400 nm whereas that of C151 is 350 nm. The fluorescence lifetimes ( τ ) and quantum yields ( ϕ f ) in CH 3 CN are typical of fluorescent dyes: TDPQ (4.2 ns, 0.8) and ETPQ (4.6 ns, 0.76). C151 showed lower τ and ϕ f 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 ϕ f for ETPQ decreased in aqueous solutions regardless of the presence of albumin or DNA. The ϕ f of TDPQ was less affected. The quantum yield of singlet oxygen ( 1 O 2 ) photosensitization ( ϕ so ) by TDPQ and ETPQ was about 7% in CH 3 CN, 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.