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Phthalocyanines and Tetrapyrazinoporphyrazines with Two Cationic Donuts: High Photodynamic Activity as a Result of Rigid Spatial Arrangement of Peripheral Substituents
B. Ghazal, M. Machacek, MA. Shalaby, V. Novakova, P. Zimcik, S. Makhseed,
Language English Country United States
Document type Journal Article
- MeSH
- Photochemotherapy MeSH
- Photosensitizing Agents chemical synthesis chemistry pharmacology MeSH
- Indoles chemical synthesis chemistry pharmacology MeSH
- Crystallography, X-Ray MeSH
- Humans MeSH
- Lysosomes metabolism MeSH
- Molecular Conformation MeSH
- Cell Line, Tumor MeSH
- Necrosis MeSH
- Porphyrins chemical synthesis chemistry pharmacology MeSH
- Pyrazoles chemical synthesis chemistry pharmacology MeSH
- Drug Screening Assays, Antitumor MeSH
- Triazoles chemical synthesis chemistry pharmacology MeSH
- Structure-Activity Relationship MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
High photodynamic activity was observed for hexadeca-cationic zinc, magnesium, and metal-free phthalocyanines (Pcs) and tetrapyrazinoporphyrazines with EC50 values as low as 5 nM (MCF-7 cells) for the best compound; this activity was several times better than that of clinically established photosensitizers verteporfin, temoporfin, S3AlOHPc, or protoporphyrin IX. This lead compound was characterized by low dark toxicity (TC50 = 369 μM), high efficiency against other cell lines (HCT 116 and HeLa), and possible activation by light above 680 nm. The excellent photodynamic activity resulted from the rigid spatial arrangement of the quaternized triazole moieties above and below the Pc core, as confirmed by X-ray crystallography. The triazole moieties thus formed two "cationic donuts" that protected the hydrophobic core against aggregation in water. The lysosomes were found to be the site of subcellular localization and were consequently the primary targets of photodynamic injury, resulting in predominantly necrotic cell death.
References provided by Crossref.org
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- $a Ghazal, Basma $u Department of Chemistry, Kuwait University , P.O. Box 5969, Safat, 13060, Kuwait.
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- $a High photodynamic activity was observed for hexadeca-cationic zinc, magnesium, and metal-free phthalocyanines (Pcs) and tetrapyrazinoporphyrazines with EC50 values as low as 5 nM (MCF-7 cells) for the best compound; this activity was several times better than that of clinically established photosensitizers verteporfin, temoporfin, S3AlOHPc, or protoporphyrin IX. This lead compound was characterized by low dark toxicity (TC50 = 369 μM), high efficiency against other cell lines (HCT 116 and HeLa), and possible activation by light above 680 nm. The excellent photodynamic activity resulted from the rigid spatial arrangement of the quaternized triazole moieties above and below the Pc core, as confirmed by X-ray crystallography. The triazole moieties thus formed two "cationic donuts" that protected the hydrophobic core against aggregation in water. The lysosomes were found to be the site of subcellular localization and were consequently the primary targets of photodynamic injury, resulting in predominantly necrotic cell death.
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