Synthesis, characterization and photodynamic activity of amino-substituted hypocrellin derivatives.
Three new hypocrellin derivatives, amino- or amino acid-substituted on the side ring of hypocrellin B (HB), were synthesized by the reactions of HB with 3-methoxypropylamine, 6-aminohexanoic acid and gamma-amino-n-butyric acid, respectively. The structures of these compounds were characterized with proton nuclear magnetic resonance spectra, infrared spectra and mass spectra. The UV-visible absorption spectra, singlet oxygen-generating quantum yield and amphiphilicities of hypocrellin derivatives were measured and compared with HB, the parent compound. These derivatives showed strong absorption in the domain of the phototherapeutic window (600-900 nm) and improved amphiphilicity. HB and the derivatives were preliminarily tested for their photodynamic effects on human oral cavity epithelial carcinoma KB cell line in vitro. Two amino acid-substituted hypocrellins showed phototoxicity to the KB cell line. At an inhibitory dosage of 50% killing only 0.51 mumol L-1 compound 3 (or 0.88 mumol L-1 compound 2) and 0.5 J cm-2 irradiation were required. The hypocrellins exhibited some dark toxicity to the KB cell line. HB and amino acid-substituted hypocrellins showed lower dark toxicity to the KB cell line than amino-substituted hypocrellins in the assessment of cell survival.
Tang
Y J
YJ
Technical Institute of Physics and Chemistry, Academia Sinica, Beijing, People's Republic of China.
Liu
H Y
HY
An
J Y
JY
Han
R
R
D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D010569:Perylene / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D010777:Photochemistry; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D011809:Quinones / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D013053:Spectrophotometry; D014407:Tumor Cells, Cultured
D017319:Photosensitizing Agents; D011809:Quinones; D010569:Perylene; C064522:hypocrellin B