Schiff Bases as Multifunctional Agents in Parkinson's Disease Therapy: A Comprehensive Review

Parkinson's disease (PD) is an irreversible neurodegenerative disorder leading to movement disorders including trembling, rigidity, and bradykinesia. The majority of these symptoms result from the death of dopaminergic neurons in the substantia nigra. Despite various pharmaceutical and surgical methods like levodopa treatment and neuromodulation being applied, none of them prevent the progression of PD. Various factors, both genetic and environmental (pesticides, head trauma, mitochondrial dysfunction), contribute to the development of this disease. Recent studies demonstrate the potential of MAO-B inhibitors to prevent dopamine degradation and oxidative stress. Schiff base derivatives are among the most interesting novel structures due to their ability to provide neuroprotection, free radical scavenging, and enzyme inhibition. The studies on isatin, benzothiazole, benzimidazole, and coumarin Schiff bases proved their potent and selective inhibition of MAO-B. Some of them demonstrate nanomolar IC50 values and promising pharmacokinetic parameters, including BBB penetration. According to the SAR, substitutions (EWG (-NO2, -Cl, -Br) and hydroxyl) increase lipophility and affinity to MAO-B. Schiff base structures have been identified as potential multi-functional platforms for the development of novel agents for neuroprotection against the effects of motor impairment and non-motor dysfunction in PD patients.