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Piperazine and Morpholine Protoporphyrin IX Derivatives Intensify Biomolecules Oxidation and Phototoxicity in Triple‐Negative Breast Cancer

Maynne Duarte Suriani Franco, Thibault Joseph William Jacques Dit Lapierre, Tarcisio Paiva Mendonça, Luiz Felipe Fernandes Peixoto, Renata Roland Teixeira, Joyce Ferreira Da Costa Guerra, Kelly Aparecida Geraldo Yoneyama Tudini, Daniele Lisboa Ribeiro, Foued Salmen Espindola, Allisson Benetti Justino, Celso de Oliveira Rezende Júnior, Tayana Mazin Tsubone

ChemMedChem · 2026

Vollständiger Abstract

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Photodynamic therapy (PDT) is a clinically established approach that relies on the localized generation of reactive oxygen species (ROS) mediated by a photosensitizer (PS), light, and molecular oxygen. Protoporphyrin IX (PpIX) is an approved PS; however, its intracellular retention is limited, factor that can alter its overall photodynamic efficiency. In this study, we report how the design of PpIX derivatives bearing piperazine (PpIX‐Pip) or morpholine (PpIX‐Morp) substituents may modulate lipophilicity, cellular uptake, oxidative stress, and phototoxicity. The photodynamic activity of these derivatives was evaluated in the aggressive triple‐negative human breast cancer cell line MDA‐MB‐231. Both derivatives showed greater time‐dependent cellular retention and enhanced photodynamic activity compared to PpIX, promoting oxidative stress, and triggering loss of mitochondrial membrane potential and caspase‐3 activation. These results highlight the impact of rational structural modification of PpIX on photodynamic efficiency and provide valuable structure–activity relationship insights for the development of improved porphyrin‐based PS for PDT.

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Autor:innen
Maynne Duarte Suriani Franco, Thibault Joseph William Jacques Dit Lapierre, Tarcisio Paiva Mendonça, Luiz Felipe Fernandes Peixoto, Renata Roland Teixeira, Joyce Ferreira Da Costa Guerra, Kelly Aparecida Geraldo Yoneyama Tudini, Daniele Lisboa Ribeiro, Foued Salmen Espindola, Allisson Benetti Justino, Celso de Oliveira Rezende Júnior, Tayana Mazin Tsubone
Quelle
ChemMedChem
Publikation
2026-01-01
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Nicht angegeben
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Nicht angegeben
ISSN / ISBN
1860-7179, 1860-7187
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Maynne Duarte Suriani Franco, Thibault Joseph William Jacques Dit Lapierre, Tarcisio Paiva Mendonça, Luiz Felipe Fernandes Peixoto, Renata Roland Teixeira, Joyce Ferreira Da Costa Guerra, Kelly Aparecida Geraldo Yoneyama Tudini, Daniele Lisboa Ribeiro, Foued Salmen Espindola, Allisson Benetti Justino, Celso de Oliveira Rezende Júnior, Tayana Mazin Tsubone (2026). Piperazine and Morpholine Protoporphyrin IX Derivatives Intensify Biomolecules Oxidation and Phototoxicity in Triple‐Negative Breast Cancer. ChemMedChem. https://doi.org/10.1002/cmdc.70471
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