Novel molecular hybrids of indoline spiropyrans and α-lipoic acid as potential photopharmacological agents: Synthesis, structure, photochromic and biological properties

Organic photochromic compounds are attracting great interest as photoswitchable components of various bioconjugates for using in photopharmacology, targeted drug delivery and bio-imaging. Here we report on the synthesis of two novel molecular hybrids of indoline spiropyrans and alpha-lipoic acid via an esterification reaction. Preliminary photochemical studies revealed photochromic activity of 5-methoxy-substituted spirocompounds in their acetonitrile solutions. Both hybrid spiropyrans along with their parent substances in the hybrids were tested for the short-term cytotoxicity on HeLa cell cultures. The results of cytotoxicity studies showed unpredictable biocompatibility of the hybrids in comparison with the parent hydroxyl-substituted spiropyrans and alpha-lipoic acid, especially at the relatively high concentration of 2 mM. Using flow cytometry, we demonstrated that the both hybrids induced antioxidant response in the model cells. After the 24 h treatment, the hybrids administered at lower (500 mu M) concentration caused suppressed cytosolic ROS and/or induced cellular thiols. At higher concentration, one of the hybrids demonstrated properties qualitatively similar to alpha-lipoic acid, yet far more strong. Together, flow cytometry results suggested that both hybrids of spiropyrans possess emergent biochemical and signaling antioxidant properties, exceeding those of alpha-lipoic acid.

Automated summary

Organic photochromic compounds are currently of great interest for use in photopharmacology, targeted drug delivery, and bio-imaging. The synthesis of two novel molecular hybrids of indoline spiropyrans and alpha-lipoic acid via an esterification reaction was reported in this study. Photochemical studies revealed the photochromic activity of the spirocompounds, while cytotoxicity tests on HeLa cell cultures showed unpredictable biocompatibility of the hybrids compared to their parent substances. Flow cytometry results demonstrated that the hybrids induced an antioxidant response in model cells, indicating emergent biochemical and signaling antioxidant properties.