Photoswitchable Phosphonate–Fullerene Hybrids with Cholinesterase Activity

Abstract

Modern progress in photopharmocology calls for new generation of compounds joining bioactivity, photoswitchable properties and high selectivity of response to light wavelength. Introduced here, phosphonate–fullerene hybrids are the first representatives of such compounds. Phosphonate–fullerene hybrids were synthesized on a base of fullerene C60 and organophosphates with the function of photoswitchable cholinesterase activity—phosphorylated thiazolotriazole and aminomalonate compounds and studied with FTIR, UV–VIS spectroscopy and IPC‐micro neurotoxin amperometric analysis. As a result of spectroscopic and bioactivity characterization, it was not only demonstrated butyrylcholinesterase (BuChE) inhibition increase in phosphonate–fullerene hybrids compared with pure phosphonates but also pronounced response of inhibition degree to laser irradiation of hybrids. It was found opposite behavior of hybrids as a result of laser irradiation—BuChE inhibition drop‐off for thiazolotriazole–fullerene and pronounced growth for aminomalonate–fullerene. The other remarkable peculiarity of presented phosphonate–fullerene hybrids is high selectivity of inhibition change degree to laser wavelength (266 or 325 nm).

All-in-One Photoactivated Inhibition of Butyrylcholinesterase Combined with Luminescence as an Activation and Localization Indicator: Carbon Quantum Dots@Phosphonate Hybrids

“…That is why photoactive phosphonates open the path to a new strategy for the treatment of these diseases based on a photopharmacological approach. Our further experiments demonstrated that fullerene@phosphonate hybrids not only retained their biological activity and photoactivation ability under the action of a laser, but also showed an increase in the inhibition difference in diverse conformational states [15].…”

Vinyl Phosphonates as Photopharmacological Agents: Laser‐Induced Cis‐Trans Isomerization and Butyrylcholinesterase Activity

“…Another strategy for the design of photoswitchable cholinesterase inhibitors can be based on the development of compounds demonstrating simultaneously two functions – photoswitching and bioactivity. It should be noting that nowadays there are only a few publications applying this approach [34–38] . Biscussi et.…”

“…The novelty of our approach is the synthesis of new compounds having both photoswitchable and bioactive properties without modification/azologization of known pharmacophores. We have previously reported on the synthesis of a series of phosphorylated arylamynomalonates and thiazolotriazol compounds with strong changes in butyrylcholinesterase (BChE) inhibition after laser stimuli [36–38] . Molecular modeling of these compounds showed an interaction with BChE enzyme centers for both isomeric states (before and after laser irradiation).…”

“…It should be noting that nowadays there are only a few publications applying this approach. [34][35][36][37][38] Biscussi et. al.…”

“…We have previously reported on the synthesis of a series of phosphorylated arylamynomalonates and thiazolotriazol compounds with strong changes in butyrylcholinesterase (BChE) inhibition after laser stimuli. [36][37][38] Molecular modeling of these compounds showed an interaction with BChE enzyme centers for both isomeric states (before and after laser irradiation). However, the interaction degree was demonstrated to be strongly dependent on the exact isomeric state.…”