Publications Repository - Gdańsk University of Technology

The group of new amide derivatives of mycophenolic acid (MPA) and selected heterocyclic amines was synthesised as potential immunosuppressive agents functioning as inosine-5'-monophosphate dehydrogenase (IMPDH) uncompetitive inhibitors. The synthesis employed uronium-type activating system (TBTU/HOBt/DIPEA) while or phosphonic acid anhydride method (T3P/Py) facilitating amides to be obtained in moderate to excellent yields without the need of phenolic group protection. Most of optimised protocols did not require complicated reaction work-ups, including chromatographic, solvent- consuming methods. The biological activity assay was performed on the T-Jurkat cell line and peripheral mononuclear blood cells (PBMCs) which are both dedicated for antiproliferative activity determination. Each of designed derivatives was characterised by reduced cytotoxicity and benzoxazole analogue revealed the most promising activity. Subsequently, an observed structure-activity relationship was discussed.

Authors

• Juliusz Walczak link open in new tab ,
• Dr Dorota Iwaszkiewicz-Grześ,
• mgr inż. Michalina Ziomkowska,
• dr hab. Magdalena Śliwka-Kaszyńska link open in new tab ,
• dr inż. Mateusz Daśko link open in new tab ,
• Piotr Trzonkowski,
• dr hab. inż. Grzegorz Cholewiński link open in new tab