Covalent and Visible-Light Photoswitchable Derivatives of the Potent Synthetic Opioid Isotonitazene and Other Nitazenes

Lahmy R, Hübner H, Gmeiner P, König B (2024)

Publication Language: English

Publication Type: Journal article

Publication year: 2024

Journal

Chemphotochem Wiley

Book Volume: 8

Article Number: e202400022

Journal Issue: 7

DOI: 10.1002/cptc.202400022

Abstract

Isotonitazene belongs to a potent class of μ-opioid receptor (μOR) ligands, known as nitazenes. The lack of knowledge surrounding this agonist and others in its class has sparked thorough re-investigations. To aid in these investigations, the purportedly covalent yet underexplored nitazene BIT was biochemically re-evaluated in this work, along with a newly synthesized analogue, Iso-BIT. Moreover, in the pursuit of understanding the mechanism, function and interactions of the μOR, this study involved developing photoswitchable nitazene derivatives as potential probe molecules. Converting known ligands into azo-containing photoswitchable derivatives offers the opportunity to modulate ligand structure with light, allowing for photocontrol of compound activity. While photocontrol of μOR activity could not be entirely achieved, photophysical evaluation of these 2-benzimidazole azo-arenes revealed a novel photoswitch scaffold that responds to visible light. Furthermore, azo-containing 2 e and 3 e emerged as promising nitazene derivatives that were able to form an exceptionally high fraction of covalent-ligand receptor complexes with wild-type μOR at physiological pH.

Authors with CRIS profile

Harald Hübner Lehrstuhl für Pharmazeutische Chemie Peter Gmeiner Lehrstuhl für Pharmazeutische Chemie

Additional Organisation(s)

FAU Forschungszentrum Neue Wirkstoffe (FAU NeW)

Involved external institutions

Universität Regensburg DE Germany (DE)

How to cite

APA:

Lahmy, R., Hübner, H., Gmeiner, P., & König, B. (2024). Covalent and Visible-Light Photoswitchable Derivatives of the Potent Synthetic Opioid Isotonitazene and Other Nitazenes. Chemphotochem, 8(7). https://doi.org/10.1002/cptc.202400022

MLA:

Lahmy, Ranit, et al. "Covalent and Visible-Light Photoswitchable Derivatives of the Potent Synthetic Opioid Isotonitazene and Other Nitazenes." Chemphotochem 8.7 (2024).

BibTeX: Download