Development of photoswitchable monoamine oxidase (MAO) inhibitors as innovative tools for studying mitochondrial oxidative stress involved in pathophysiological processes.
Mitochondrial oxidative stress is considered as a triggering or potentiating factor in many diseases (e.g., cancers, neurodegenerative and cardiovascular diseases), and oxidases, such as the monoamine oxidases (MAO) present in the mitochondria, participate in the development of this oxidative stress via the production of reactive oxygen species (ROS).
Photopharmacology is an emerging approach in medicine based on the administration of a photoswitchable drug in combination with light irradiation to provide spatiotemporal control of the activity of a bioactive molecule. Therefore, this concept is useful for therapeutic applications and a research tool to study cellular mechanisms.
Based on this concept, the objective of this internship is to develop photoswitchable MAO inhibitors as novel tools for the study of pathophysiological processes involving mitochondrial oxidative stress.
Keywords: Medicinal chemistry; organic chemistry; UV-Vis spectroscopy; docking
References: J. Med. Chem. 2020, 63, 11436-11447 ; Chem. Rev. 2018, 118, 10710-10747 ; Angew. Chem. Int. Ed. 2016, 55, 10978-10999.
Starting date: January-February 2022
Duration: 6 months
Location: Laboratory CiTCoM CNRS UMR 8038, Team « Medicinal chemistry and translational research » (ERL INSERM U 1268), 4 Avenue de l’Observatoire, 75270 Paris Cedex 06, France
Applications should be sent by e-mail to Pr. Ludovic Jean ludovic.jean1@parisdescartes.fr, including a CV, a cover letter, a recommendation letter and transcripts of master 1