1. Highly Phototoxic Transplatin‐Modified Distyryl‐BODIPY Photosensitizers for Photodynamic Therapy
- Author
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Padrutt, Roxane, Babu, Vipin, Klingler, Simon, Kalt, Martina, Schumer, Frank, Anania, Maria I, Schneider, Lukas, Spingler, Bernhard, University of Zurich, and Spingler, Bernhard
- Subjects
Boron Compounds ,10120 Department of Chemistry ,1303 Biochemistry ,Cell Survival ,medicine.medical_treatment ,Antineoplastic Agents ,Photodynamic therapy ,Photochemistry ,Toxicology and Pharmaceutics ,01 natural sciences ,Biochemistry ,3000 General Pharmacology, Toxicology and Pharmaceutics ,Structure-Activity Relationship ,chemistry.chemical_compound ,540 Chemistry ,General Pharmacology ,Drug Discovery ,medicine ,Humans ,Photosensitizer ,General Pharmacology, Toxicology and Pharmaceutics ,Cell Proliferation ,Pharmacology ,Photosensitizing Agents ,Dose-Response Relationship, Drug ,Molecular Structure ,Singlet Oxygen ,010405 organic chemistry ,Chemistry ,Singlet oxygen ,3002 Drug Discovery ,Organic Chemistry ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,3004 Pharmacology ,Intersystem crossing ,Photochemotherapy ,1313 Molecular Medicine ,Intramolecular force ,Molecular Medicine ,Cisplatin ,Drug Screening Assays, Antitumor ,BODIPY ,Phototoxicity ,HeLa Cells ,1605 Organic Chemistry - Abstract
We report the synthesis of the first transplatin-BODIPY conjugates for application in photodynamic therapy (PDT). The distyryl BODIPYs containing two iodine atoms were designed to absorb in the red region, easily undergo intersystem crossing for efficient singlet oxygen generation, and additionally offer the possibility for coordination with mono-activated transplatin. We were able to demonstrate that coordination of the BODIPYs with a mono-activated transplatin increases the phototoxic index of the photosensitizers significantly, giving rise to highly phototoxic distyryl BODIPY derivatives, of which one was shown to have the highest ever reported phototoxic index against any cell line. Furthermore, the photophysical mechanism of singlet oxygen generation in distyryl BODIPYs undergoing intramolecular charge transfer was studied experimentally and using time-dependent density functional theory.
- Published
- 2020
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