Core-modified porphyrins. Part 5: Electronic effects on photophysical and biological properties in vitro.

Abstract

21,23-Dithiaporphyrins 2-11 were prepared as analogues of 5,20-diphenyl-10,15-bis(4-carboxylatomethoxy)phenyl-21,23-dithiaporphyrin 1 to examine the impact of electronic properties at the 5- and 20-meso-positions. The effects of the electronic properties at the meso-rings were not significant with respect to absorption spectra, quantum yields for the generation of singlet oxygen and for fluorescence. While some differences were noted in the n-octanol/pH 7.4 buffer partition coefficient, log D(7.4), among the compounds, log D(7.4) did not critically influence the cellular uptake or phototoxicity. None of the dithiaporphyrins 1-11 displayed dark toxicity at concentrations up to 1 x 10(-5) M. Once irradiated with 5 J cm(-2) of 350-750 nm light, five porphyrins 2, 3, 5, 6, and 8 killed over 80% of R3230AC rat mammary adenocarcinoma cells at 5 x 10(-7) M photosensitizer. Among these five, compound 3 bearing 5-phenyl and 20-(4-fluorophenyl) substituents was the most potent photosensitizer toward R3230AC cells showing 67% cell kill at 1 x 10(-7) M 3. Bulky substituents at the 5- and 20-positions gave photosensitizers with minimal phototoxicity.

• Authors: Youngjae You, Scott L Gibson, Michael R Detty
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 13 Issue 21 Pg. 5968-80 (Nov 01 2005) ISSN: 0968-0896 [Print] England
• PMID: 16084729 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Carboxylic Acids
• Photosensitizing Agents
• Porphyrins

Topics

• Animals
• Carboxylic Acids (chemical synthesis, chemistry)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Molecular Structure
• Photochemistry
• Photosensitizing Agents (chemistry, pharmacology)
• Porphyrins (chemistry, pharmacology)
• Rats
• Spectrum Analysis
• Static Electricity