Mitochondria-Targeting Selenophene-Modified BODIPY-Based Photosensitizers for the Treatment of Hypoxic Cancer Cells
| Autor: | Safacan Kolemen, Toghrul Almammadov, Gorkem Gunbas, Gurcan Gunaydin, M. Emre Gedik, Osman Karaman |
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| Rok vydání: | 2019 |
| Předmět: |
Boron Compounds
Cell Survival medicine.medical_treatment Photodynamic therapy Antineoplastic Agents Mitochondrion 01 natural sciences Biochemistry chemistry.chemical_compound Mice Structure-Activity Relationship Organoselenium Compounds Drug Discovery medicine Animals Humans General Pharmacology Toxicology and Pharmaceutics Inner mitochondrial membrane Cell Proliferation Pharmacology Photosensitizing Agents Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Singlet oxygen Organic Chemistry Highly selective Cell Hypoxia 0104 chemical sciences Mitochondria 010404 medicinal & biomolecular chemistry chemistry Photochemotherapy Cancer cell Biophysics NIH 3T3 Cells Molecular Medicine BODIPY Drug Screening Assays Antitumor HeLa Cells |
| Zdroj: | ChemMedChem. 14(22) |
| ISSN: | 1860-7187 |
| Popis: | Two red-absorbing, water-soluble and mitochondria (MT)-targeting selenophene-substituted BODIPY-based photosensitizers (PSs) were realized (BOD-Se, BOD-Se-I), and their potential as photodynamic therapy (PDT) agents were evaluated. BOD-Se-I showed higher 1 O2 generation yield thanks to the enhanced heavy-atom effect, and this derivative was further tested in detail in cell culture studies under both normoxic and hypoxic conditions. BOD-Se-I not only effectively functioned under hypoxic conditions, but also showed highly selective photocytotoxicity towards cancer cells. The selectivity is believed to arise from differences in mitochondrial membrane potentials of healthy and cancerous cells. To the best of our knowledge, this marks the first example of a MT-targeted BODIPY PS that functions under hypoxic conditions. Remarkably, thanks to the design strategy, all these properties where realized by a compound that was synthesized in only five steps with 32 % overall yield. Hence, this material holds great promise for the realization of next-generation PDT drugs for the treatment of hypoxic solid tumors. |
| Databáze: | OpenAIRE |
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