A novel elsinochrome A derivative: a study of drug delivery and photodynamic activity.
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.
Zhang
Yang
Y
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, P. R. China.
Xie
Jie
J
Zhang
Luyong
L
Li
Cong
C
Chen
Hongxia
H
Gu
Ying
Y
Zhao
Jingquan
J
D016227:Benzoquinones / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D017665:Hydroxyl Radical / Q000737:chemistry / Q000378:metabolism; D010569:Perylene / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000494:pharmacology; D011809:Quinones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D026082:Singlet Oxygen / Q000737:chemistry / Q000378:metabolism; D013053:Spectrophotometry
D016227:Benzoquinones; D017319:Photosensitizing Agents; D011809:Quinones; D026082:Singlet Oxygen; C062775:elsinochrome A; C025232:semiquinone radicals; D017665:Hydroxyl Radical; D010569:Perylene; C064522:hypocrellin B