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A novel elsinochrome A derivative: a study of drug delivery and photodynamic activity

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Abstract

Elsinochrome A (EA) possesses the highest singlet-oxygen quantum yield (0.98) amongst the perilenoquinoid pigments and may be suitable as a phototherapeutic drug. However, there have been virtually no studies into its medicinal applications. Based on the analysis of chemical derivatives of hypocrellins (the same family as EA), 5-(3-mercapto-1-propanesulfonic acid)-substituted elsinochrome A (MPEA) with an amphiphilicity was designed and synthesized by considering drug delivery and biological activity requirements. MPEA possesses a water solubility of 5.1 mg mL-1, which is just sufficient to enable dissolution at a clinically acceptable concentration, while its partition coefficient (n-octanol/phosphate buffered saline) of 7 guarantees affinity to biological targets. MPEA could photogenerate semiquinone anion radicals and reactive oxygen species, especially singlet oxygen, at a yield of 0.73, which approaches that for hypocrellin B. Biological tests confirmed that the photodynamic activity of MPEA was as high as 60% of that of its parent EA, which is significantly higher than that of most other photosensitizers.

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Abbreviations

DMPO:

5,5-Dimethyl-1-pyrroline-N-oxide

SOD:

Superoxide dismutase

NADH:

Reduced nicotinamideadenine dinucleotide

DMSO:

Dimethyl sulfoxide

PBS:

Phosphate buffered saline

TEMPO:

2,2,6,6-Tetramethyl-4-piperidone-N-oxyl radical

TEMP:

2,6,6-Tetramethyl-4-piperidone

EPR:

Electron paramagnetic resonance

DPA:

9,10-Diphenylanthracene

DABCO:

1,4-Diazabicyclo[2,2,2]octane

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Authors and Affiliations

  1. Beijing National Laboratory for Molecular Sciences (BNLMS), Key Laboratory of Photochemistry, Institute of Chemistry, Chinese Academy of Sciences, P. O. Box 101, No. 2, 1st North Street, Zhongguancun, Beijing, 100190, China

    Yang Zhang, Jie Xie & Jingquan Zhao

  2. Department of Laser Medicine, Chinese PLA General Hospital, No. 28, Fuxing Road, Beijing, 100853, China

    Luyong Zhang, Hongxia Chen & Ying Gu

  3. Department of Applied Chemistry, Yunnan University, Kunming, 650091, China

    Cong Li

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  1. Yang Zhang
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  2. Jie Xie
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  3. Luyong Zhang
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  4. Cong Li
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  5. Hongxia Chen
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  6. Ying Gu
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  7. Jingquan Zhao
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Correspondence to Ying Gu or Jingquan Zhao.

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Zhang, Y., Xie, J., Zhang, L. et al. A novel elsinochrome A derivative: a study of drug delivery and photodynamic activity. Photochem Photobiol Sci 8, 1676–1682 (2009). https://doi.org/10.1039/b9pp00046a

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