The in vitro photodynamic activity, photophysical and photochemical research of a novel chlorophyll-derived photosensitizer

Chlorophyll has always been used as the leading compound for photodynamic therapy drug development. In this paper, a novel methyl pyropheophorbide-a- derived photosensitizer, 3-acetyl-3-devinyl-13(1)-dicyanomethylene-pyropheophorbide-a was synthesized through modifications at C-13(1), C-3, and C-17 positions of methyl pyropheophorbide-a. The compound exhibited a longer wavelength absorption at 713 nm (in methanol) than that of methyl pyropheophorbide-a (667 nm) due to the enlarged the aromatic conjugation system by dicyanomethylene, allowing it to be potential in deep tumor treatment. Moreover, benefiting from the carboxylic group at C-17 and the acetyl group at C-3, the title compound was endowed with better water solubility than that of methyl pyropheophorbide-a. Detailed in vitro photodynamic therapy research showed ADCPPa could be uptaken by cancer cells successfully and killed the cancer cells more efficiently than the leading compound methyl pyropheophorbide-a under light (light dose 10 J/cm(2)) due to the high singlet oxygen quantum yield (65.98%). The excellent anti-photobleaching ability (degradation rate 1.6% in 10 min) also boosted its potential in practical application. In addition, the research has disclosed that during photochemical processes of photodynamic therapy, the formation of singlet oxygen after photodynamic therapy treatment played a major role, comparing with the formation of superoxide anion and radicals. Finally, the real time quantitative polymerase chain reaction (RT-qPCR) experiments have showed that the target compound has important regulating effect on expression of CDK2 and Survivin, consequently leading to apoptosis and cell death.