Medicinal Chemistry Research

, Volume 26, Issue 10, pp 2639–2652 | Cite as

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

Original Research
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Abstract

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-131-dicyanomethylene-pyropheophorbide-a was synthesized through modifications at C-131, 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/cm2) 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.

Keywords

Photodynamic therapy Methyl pyropheophorbide-a Dicyanomethylene Antitumor 

Notes

Acknowledgements

Financial support of this research was provided by National Natural Science Foundation of China (No. 20972036, 21272048, 21471041), the Natural Science Foundation of Heilongjiang Province (No.B20913), the Program for Scientific Technological Innovation Team Construction in the Universities of Heilongjiang Province (No. 211TD010), the Scientific Research Fund of Heilongjiang Provincial Education Department (No.12531194), the Natural Science Youth Foundation of Heilongjiang Province (No. QC2016011) and the Innovation Fund for Graduate Students of Harbin Normal University

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

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© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.College of Life Science and TechnologyHarbin Normal UniversityHarbinChina
  2. 2.College of Chemistry & Chemical EngineeringHarbin Normal UniversityHarbinChina

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