Xanthine-Dopamine Hybrid Molecules as Multitarget Drugs with Potential for the Treatment of Neurodegenerative Diseases.

ABSTRACT: Multitarget drugs based on a hybrid dopamine-xanthine core were designed as potential drug candidates for the treatment of neurodegenerative diseases. Monoamine oxidase B (MAO-B) inhibitors with significant ancillary A_2A adenosine receptor (A_2AAR) antagonistic properties were further developed to exhibit additional phosphodiesterase-4 and -10 (PDE4/10) inhibition and/or dopamine D₂ receptor (D₂R) agonistic activity. While all of the designed compounds showed MAO-B inhibition in the nanomolar range mostly combined with submicromolar A_2AAR affinity, significant enhancement of PDE-inhibitory and D₂R-agonistic activity was additionally reached for some compounds through various structural modifications. The final multitarget dru

SUBMITTER: Zaluski M 

PROVIDER: S-EPMC10377586 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature