In:
Organic & Biomolecular Chemistry, Royal Society of Chemistry (RSC), Vol. 20, No. 39 ( 2022), p. 7787-7794
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
1477-0520
,
1477-0539
Sprache:
Englisch
Verlag:
Royal Society of Chemistry (RSC)
Publikationsdatum:
2022
ZDB Id:
2097583-1
