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PEGylated Purpurin 18 with Improved Solubility: Potent Compounds for Photodynamic Therapy of Cancer

Purpurin 18 derivatives with a polyethylene glycol (PEG) linker were synthesized as novel photosensitizers (PSs) with the goal of using them in photodynamic therapy (PDT) for cancer. These compounds, derived from a second-generation PS, exhibit absorption at long wavelengths; considerable singlet ox...

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Autores principales: Pavlíčková, Vladimíra, Rimpelová, Silvie, Jurášek, Michal, Záruba, Kamil, Fähnrich, Jan, Křížová, Ivana, Bejček, Jiří, Rottnerová, Zdeňka, Spiwok, Vojtěch, Drašar, Pavel, Ruml, Tomáš
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943672/
https://www.ncbi.nlm.nih.gov/pubmed/31817655
http://dx.doi.org/10.3390/molecules24244477
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author Pavlíčková, Vladimíra
Rimpelová, Silvie
Jurášek, Michal
Záruba, Kamil
Fähnrich, Jan
Křížová, Ivana
Bejček, Jiří
Rottnerová, Zdeňka
Spiwok, Vojtěch
Drašar, Pavel
Ruml, Tomáš
author_facet Pavlíčková, Vladimíra
Rimpelová, Silvie
Jurášek, Michal
Záruba, Kamil
Fähnrich, Jan
Křížová, Ivana
Bejček, Jiří
Rottnerová, Zdeňka
Spiwok, Vojtěch
Drašar, Pavel
Ruml, Tomáš
author_sort Pavlíčková, Vladimíra
collection PubMed
description Purpurin 18 derivatives with a polyethylene glycol (PEG) linker were synthesized as novel photosensitizers (PSs) with the goal of using them in photodynamic therapy (PDT) for cancer. These compounds, derived from a second-generation PS, exhibit absorption at long wavelengths; considerable singlet oxygen generation and, in contrast to purpurin 18, have higher hydrophilicity due to decreased logP. Together, these properties make them potentially ideal PSs. To verify this, we screened the developed compounds for cell uptake, intracellular localization, antitumor activity and induced cell death type. All of the tested compounds were taken up into cancer cells of various origin and localized in organelles known to be important PDT targets, specifically, mitochondria and the endoplasmic reticulum. The incorporation of a zinc ion and PEGylation significantly enhanced the photosensitizing efficacy, decreasing IC(50) (half maximal inhibitory compound concentration) in HeLa cells by up to 170 times compared with the parental purpurin 18. At effective PDT concentrations, the predominant type of induced cell death was apoptosis. Overall, our results show that the PEGylated derivatives presented have significant potential as novel PSs with substantially augmented phototoxicity for application in the PDT of cervical, prostate, pancreatic and breast cancer.
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spelling pubmed-69436722020-01-10 PEGylated Purpurin 18 with Improved Solubility: Potent Compounds for Photodynamic Therapy of Cancer Pavlíčková, Vladimíra Rimpelová, Silvie Jurášek, Michal Záruba, Kamil Fähnrich, Jan Křížová, Ivana Bejček, Jiří Rottnerová, Zdeňka Spiwok, Vojtěch Drašar, Pavel Ruml, Tomáš Molecules Article Purpurin 18 derivatives with a polyethylene glycol (PEG) linker were synthesized as novel photosensitizers (PSs) with the goal of using them in photodynamic therapy (PDT) for cancer. These compounds, derived from a second-generation PS, exhibit absorption at long wavelengths; considerable singlet oxygen generation and, in contrast to purpurin 18, have higher hydrophilicity due to decreased logP. Together, these properties make them potentially ideal PSs. To verify this, we screened the developed compounds for cell uptake, intracellular localization, antitumor activity and induced cell death type. All of the tested compounds were taken up into cancer cells of various origin and localized in organelles known to be important PDT targets, specifically, mitochondria and the endoplasmic reticulum. The incorporation of a zinc ion and PEGylation significantly enhanced the photosensitizing efficacy, decreasing IC(50) (half maximal inhibitory compound concentration) in HeLa cells by up to 170 times compared with the parental purpurin 18. At effective PDT concentrations, the predominant type of induced cell death was apoptosis. Overall, our results show that the PEGylated derivatives presented have significant potential as novel PSs with substantially augmented phototoxicity for application in the PDT of cervical, prostate, pancreatic and breast cancer. MDPI 2019-12-06 /pmc/articles/PMC6943672/ /pubmed/31817655 http://dx.doi.org/10.3390/molecules24244477 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pavlíčková, Vladimíra
Rimpelová, Silvie
Jurášek, Michal
Záruba, Kamil
Fähnrich, Jan
Křížová, Ivana
Bejček, Jiří
Rottnerová, Zdeňka
Spiwok, Vojtěch
Drašar, Pavel
Ruml, Tomáš
PEGylated Purpurin 18 with Improved Solubility: Potent Compounds for Photodynamic Therapy of Cancer
title PEGylated Purpurin 18 with Improved Solubility: Potent Compounds for Photodynamic Therapy of Cancer
title_full PEGylated Purpurin 18 with Improved Solubility: Potent Compounds for Photodynamic Therapy of Cancer
title_fullStr PEGylated Purpurin 18 with Improved Solubility: Potent Compounds for Photodynamic Therapy of Cancer
title_full_unstemmed PEGylated Purpurin 18 with Improved Solubility: Potent Compounds for Photodynamic Therapy of Cancer
title_short PEGylated Purpurin 18 with Improved Solubility: Potent Compounds for Photodynamic Therapy of Cancer
title_sort pegylated purpurin 18 with improved solubility: potent compounds for photodynamic therapy of cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943672/
https://www.ncbi.nlm.nih.gov/pubmed/31817655
http://dx.doi.org/10.3390/molecules24244477
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