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

Abstract

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 α-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 µM) 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.

Keywords: Cytotoxicity; Flow cytometry; Molecular switches; Photochromism; Photopharmacology; Single-crystal X-ray analysis; Spiropyrans; α-Lipoic acid.