Structure Optimization of 21, 23-Core-Modified Porphyrins Absorbing Long-Wavelength Light as Potential Photosensitizers Against Breast Cancer Cells
Abstract
The main subjects of year one were to prepare the diverse structures of core-modified porphyrins, and to examine their physical properties and in vitro biological activities. Twenty five dithiaporphyrin compounds were synthesized with different features in size, symmetry, and electronic property at meso-aromatic groups of the porphyrins. These structural analogues had similar absorption maxima (-700 nm) and quantum yields of singlet oxygen generation (^0.8). However, these structural changes showed striking difference in biological activities. Thirteen compounds expressed >50 % cell kill at 0.5 micrometers and 5-phenyl- 20- (2-thienyl) -10, 15-bis (4-carboxylatomethoxyphenyl) -21,23-dithiaporphyrin was most potent displaying 68% cell kill at 0.1 micrometers with 5 microjoules/squared of light. In a mechanistic study, the porphyrin inhibited cytochrome c oxidase although it did not initially localize in the mitochondria. This enzyme damage can be explained by re-localization of porphyrin during irradiation. Interestingly, the induction of apoptotic cell death with the porphyrin depended on the incubation time with the photosensitizer and its concentration. Longer incubation time with the sensitizer (24 hr) at an appropriate concentration (0.2 micrometers) gave the most apoptosis. Base on the localization pattern with 24 hr incubation and consequent apoptotic process by PDT, there might be a target site inside the cell to trigger.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2005
- Accession Number
- ADA435286
Entities
People
- Youngjae You
Organizations
- State University of New York at Albany