Photoinduced cytotoxicity of photochromic symmetric diarylethene derivatives: the relation of structure and cytotoxicity

Abstract

Photopharmacology has been attracting attention for the development of drugs with fewer side effects and toxicity by introducing a photoswitch structure in the drug and controlling its spatiotemporal effects by...

Phototunable Cell Killing by Photochromic Diarylethene of Thiazoyl and Thienyl Derivatives

“…The first evaluation was to investigate the photoresponsivity, reversibility, and thermal stability of the derivatives in polar solvents, including water, for use in cells. For the molecule, we chose derivative 1 having two thiazole rings in the molecule, which had the highest photoinduced cytotoxicity in our previous works. , The absorption maxima of the open- ( 1o ) and closed-ring ( 1c ) isomers of 1 in polar solvents containing water were observed at almost the same wavelengths as in water-free organic solvent, which was previously reported (Supporting Information, Figure S2). For the photostationary state (PSS) by UV light (λ = 365 nm) irradiation under these conditions, the generation of the closed-ring form is more than 70%.…”

“…To clarify the mechanism of the photoinduced cell death, photoinduced cytotoxicities were investigated by derivative 1 having two thiazole rings in the molecule (Figure ), which had the highest photoinduced cytotoxicity in our previous works. , The cytotoxicity depends not only on the DAE concentration in the culture medium but also on the initial amount of seeded cells; more cytotoxicity appears in the case of a smaller amount of seeded cells even at a constant DAE concentration in the culture medium. This observation suggests that the DAE partitions much more extensively into the cells than in the culture medium.…”

“…In the case of 1c , shrinkage and rounding of HeLa cells in the area irradiated by blue light (λ = 436 nm) were observed at LLC of 0.05 ppm (equivalent to 50 μg/L and 1 nM) . Cell shrinkage and cell rounding are known as characteristics of apoptotic cells, and we have reported that 1c -induced cell death is caused by apoptosis. , These photoinduced cytotoxicities were caused at lower concentrations than the toxicity without light irradiation (Supporting Information, Table S2). In particular, the photoinduced cytotoxicity of 1c at very low doses offers very attractive potential for its application to cancer therapy.…”

“…Displacement of EB from the fluorescent EB-DNA adduct by a DNA-interacting molecule can induce fluorescence quenching. 8,16,23,24 Fluorescence spectra were monitored at constant concentrations of DNA and EB (3.9 nM bp −1 and 75 μM, respectively) while increasing the amounts of DAEs (in the range of 0−25 μM: Table S3) (see Experimental Section DNA (Figure 3d and Supporting Information, Figure S5 and Table S4).…”

“…Subsequently, we studied the relationship between nitrogen-containing heterocycles (thiazole and pyridine rings) in symmetric DAE molecules and photoinduced cytotoxicity. This allowed us to then conceive a molecular design with a simple structure that could be precisely controlled using a molecular switch mechanism at the molecular level . However, the data collected so far is not sufficient to understand the mechanism of action and wavelength dependence of photoinduced cytotoxicity.…”