Mohamed Ali Dridi PhD defense - Campus De Beaulieu, ISCR, Bât. 10B, Salle 160

Organic Chemistry & Interfaces (COrInt) team

Abstract
This thesis work focuses on the synthesis and biological evaluation of analogues of the GSK-3 inhibitors MH-124 and CD-07 through different pharmacomodulation strategies to improve their affinity and selectivity toward the GSK-3α isoform. In the first part of this work, the introduction of a phosphorus atom within the oxazole core was investigated to reach a new family of phosphorus-containing heterocycles. Due to their moderate inhibitory properties, we next focused our attention on other families. Building on the previous work of the team on reference inhibitors, the second part of this study was therefore dedicated to the synthesis of original derivatives by modifying different structural features of these molecules. Assays on kinases revealed a high affinity for GSK-3, some compounds even demonstrating antiproliferative activities against cancer cells. Finally, the last part of this work focused on the synthesis of a new series of phenanthrolinones. Their inhibitory properties were evaluated, leading to the identification of a compound exhibiting interesting selectivity toward the CLK1 kinase, representing the most significant outcome obtained within this series.

Jury
Franck SUZENET, Professor, University of Orleans, / Reviewer
Mohamed Lotfi EFRIT, Professor, University of Tunis El Manar / Reviewer
Corinne FRUIT, Professor, University of Rouen / Examiner
Ali SAMARAT, Professor, University of Carthage / Examiner

Supervisors
Florence MONGIN, Professor, University of Rennes, ISCR
Soufiane TOUIL, Professor, University of Carthage
William ERB, Associate Professor, University of Rennes, ISCR

Contacts
Florence Mongin, florence.mongin@univ-rennes.fr
William Erb, william.erb@univ-rennes.fr