ABSTRACT
Six methyl pheophorbide-a derivatives were prepared by linking a tryptamine side chain at the C-131 , C-152 and C-173 positions of pheophorbide-a. Prepared conjugates were characterized and evaluated for their photocytotoxicity against A549 cells. The conjugate 6 a with strong absorption at 413â nm (Soret band), 663-671â nm (Q bands) and comparable fluorescence quantum yield (0.26) was found to exhibit significant cytotoxicity (659â nM). Molecular integration of pheophorbide-a and tryptamines showed synergistic effects as the most potent conjugate 6 a was identified with enhanced photocytotoxicity when compared to methyl pheophorbide-a. The conjugate 6 a was smoothly taken up by A549 cells and exhibited intracellular localization predominantly to lysosome in the cytoplasm. Upon photoirradiation 6 a generated singlet oxygen to show potent cytotoxicity toward A549 cells.
Subject(s)
Photochemotherapy , Photosensitizing Agents , Photosensitizing Agents/chemistry , Cell Line, Tumor , Tryptamines/pharmacologyABSTRACT
We have developed an efficient protocol for the synthesis of meso,ß-pyrrolo- and indolo[1,2-a]quinoxalino-fused porphyrin systems 7-9 by PIFA-promoted intramolecular oxidative cyclization of easily accessible meso-pyrrolo- and indolo[1,2-a]quinoxalino-appended porphyrins 6a-j. The absorption spectra of meso,ß-pyrrolo- and indolo[1,2-a]quinoxalino-fused porphyrins 7-9 displayed bathochromic shifted (100-150 nm) and broadened Soret bands and Q bands in addition to intense band near IR region. The indolo[1,2-a]quinoxalino-fused porphyrin 9bZn with lower fluorescence quantum yield (0.003) and reduced energy gap (â¼1.3 eV) was found to sensitize singlet oxygen effectively.