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Synthesis of Red-Light-Responsive Pheophorbide-a Tryptamine Conjugated Photosensitizers for Photodynamic Therapy |
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| Authors: | Taur Prakash Pandurang Bintu Kumar Narshimha Verma Debabrata Ghosh Dastidar Risa Yamada Tatsuya Nishihara Prof Kazuhito Tanabe Prof Dalip Kumar |
| Affiliation: | 1. Department of Chemistry, Birla Institute of Technology and Science, Pilani, 333031 Rajasthan, India
Contribution: Methodology (lead), Writing - original draft (lead);2. Department of Chemistry, Birla Institute of Technology and Science, Pilani, 333031 Rajasthan, India;3. Department of Chemistry, Birla Institute of Technology and Science, Pilani, 333031 Rajasthan, India Contribution: Methodology (supporting), Writing - review & editing (supporting);4. Guru Nanak Institute of Pharmaceutical Science & Technology, Panihati, Kolkata, 700114 West Bengal, India;5. College of Science and Engineering, Aoyama Gakuin University, Sagamihara, 252-5258 Japan |
| Abstract: | Six methyl pheophorbide-a derivatives were prepared by linking a tryptamine side chain at the C-13 1 , C-15 2 and C-17 3 positions of pheophorbide-a. P repared conjugates were characterized and evaluated for their photocytotoxicity against A549 cells. The conjugate 6 a with strong absorption at 413 nm (Soret band), 663–671 nm (Q bands) and comparable fluorescence quantum yield (0.26) was found to exhibit significant cytotoxicity (659 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. T he 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. |
| Keywords: | pheophorbide-a tryptamine conjugate photosensitizers porphyrinoids lysosome localization photodynamic therapy |