Details

Autor(en) / Beteiligte

• Bilski, Piotr J.
• Risek, Boris
• Chignell, Colin F.
• Schrader, William T.

Titel

Photocytotoxicity of the Fluorescent Nonsteroidal Androgen Receptor Ligand TDPQ

Ist Teil von

• Photochemistry and photobiology, 2009-09, Vol.85 (5), p.1225-1232

Ort / Verlag

Oxford, UK: Blackwell Publishing Ltd

Erscheinungsjahr

2009

Quelle

Wiley Online Journals

Beschreibungen/Notizen

• 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 lower τ and ϕf 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 ϕf for ETPQ decreased in aqueous solutions regardless of the presence of albumin or DNA. The ϕf of 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.