Synthesis, Characterization, and Biological Evaluation of a Porphyrin-Based Photosensitizer and Its Isomer for Effective Photodynamic Therapy against Breast Cancer

A photosensitizer with high phototoxicity, low dark toxicity, and good water solubility is crucial for effective photodynamic therapy (PDT). In this study, a novel class of porphyrin-based water-soluble derivative and its isomers, named photohexer-1 (P-1) and photohexer-2 (P-2), were synthesized and...

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Veröffentlicht in:Journal of medicinal chemistry 2018-08, Vol.61 (16), p.7189-7201
Hauptverfasser: Feng, Xiaolan, Shi, Yin, Xie, Lifen, Zhang, Kun, Wang, Xiaobing, Liu, Quanhong, Wang, Pan
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Sprache:eng
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Zusammenfassung:A photosensitizer with high phototoxicity, low dark toxicity, and good water solubility is crucial for effective photodynamic therapy (PDT). In this study, a novel class of porphyrin-based water-soluble derivative and its isomers, named photohexer-1 (P-1) and photohexer-2 (P-2), were synthesized and investigated for anticancer activity. Both of the isomers, P-1 and P-2, could be utilized as potential sensitizers for PDT not only owing to their definite constituents but predominantly due to their good absorption in the phototherapeutic window and high generation of intracellular ROS. Therein, P-2 exhibited stronger phototoxicity against breast cancer cells with weaker dark toxicity than P-1; however, both P-1 and P-2 were highly phototoxic as compared to their homologous compound, hematoporphyrin monomethyl ether (HMME). These findings were consistent with the antitumor efficacy in vivo. Moreover, P-1 and P-2 could both effectively localize in multiple subcellular organelles, triggering increased cellular apoptosis or necrosis under laser irradiation as compared to HMME. In conclusion, the findings of the study suggest that the two highly water-soluble porphyrin derivatives may serve as promising putative photosensitizers for improving the therapeutic efficiency of PDT.
ISSN:0022-2623
1520-4804
DOI:10.1021/acs.jmedchem.8b00547