Self-reporting styrylthiazolium photopharmaceuticals: mitochondrial localisation as well as SAR drive biological activity
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
Abstract
Novel photoswitches offering features complementary to the well-established azobenzenes are increasingly driving high-precision research in cellular photopharmacology. Styrylthiazolium (StyTz) and styrylbenzothiazolium (StyBtz) are cellularly untested E/Z-isomerisation photoswitches which are nearly isosteric to azobenzenes, but have distinct properties: including ca. 60 nm red-shifted π → π* absorption, self-reporting fluorescence, Z → E relaxation on typical biological timescales, and decent solubility (positive charge). We tested StyTz and StyBtz for their potential as photopharmaceutical scaffolds, by applying them to photocontrol microtubule dynamics. They light-specifically disrupt microtubule network architecture and block cell proliferation: yet, testing lead compound StyBtz2 for its molecular mechanism of action showed that it did not inhibit microtubule dynamics. Using its self-reporting fluorescence, we tracked its localisation in live cells and observed accumulation of E-StyBtz2 into mitochondria; during prolonged illumination, it was released into the cytosol, and blebbing and cell death were observed. We interpret this as light-dependent rupturing of mitochondria on acute timescales. We conclude that StyTz/StyBtz can be interesting photopharmaceutical scaffolds for addressing mitochondrial, rather than cytosolic, targets.
Details
Original language | English |
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Pages (from-to) | 7787-7794 |
Number of pages | 8 |
Journal | Organic & biomolecular chemistry |
Volume | 20 |
Issue number | 39 |
Publication status | Published - 26 Sept 2022 |
Peer-reviewed | Yes |
Externally published | Yes |
External IDs
Scopus | 85139739697 |
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