Photoswitchable ligands as tool to modulate biological activity

In contrast to other tools for the control biological processes, light does not cause contamination of the studied object, has low or negligible toxicity at long wavelengths and can be delivered with very high spatial and temporal precision. The use of light in conjunction with a pharmacological approach gives rise to the ever-expanding field of photopharmacology. Indeed, as pharmacodynamics and pharmacokinetic properties of drugs are directly related to their molecular structure, a photoinduced structural change in a photoswitchable drug can result in the activation/deactivation or modulation of the drug-target interaction and biological functions only in the region where light is provided. To date, photopharmacology has been extensively used to manipulate biological activity at the cellular level by targeting ion channels, G protein-coupled receptors, enzymes and protein-protein interactions [1]. One of the major advancements in photopharmacology would be to develop drugs that can be photoswitched using low energy light, which is less scattered in tissue and can penetrate deeper in the body. To this end, a molecular structure should be designed to ensure photoconversion by red or infrared light. Here, we present the molecular design of a novel γ- aminobutyric acid type A receptors (GABAARs) ligand derivative that displays photochromic properties with red light and we discuss its chemical as well as its photoisomerization and photopharmacological properties [2]. References 1. Eli S., Castagna R., Mapelli M., Parisini E. (2022) Recent Approaches to the Identification of Novel Microtubule-Targeting Agents. Front. Mol. Biosci. 9:841777. 2. Castagna R. et al. (2022) A donor-acceptor Stenhouse adduct displaying reversible photoswitching in water and neuronal activity chemRxiv doi: 10.26434/chemrxiv-2022-0ps7t.