2-Iminothiazolidine as a potential antioxidant and inhibitor of monoamine oxidase and acetylcholinesterase: in vitro assays and ADME/T predictions

Oxidative stress (OS), from an imbalance between reactive species (RS) and antioxidants, can damage macromolecules. Monoamine oxidases A and B (MAO-A, MAO-B) are mediators of OS and can also affect acetylcholinesterase (AChE), contributing to neuronal dysfunction in neurodegenerative and psychiatric disorders. Accordingly, the antioxidant and enzymatic inhibitory potential of methyl 3-amino-2-imino-4-(4-nitrobenzyl)-1,3-thiazolidine-4-carboxylate (thiazolidine 49) was evaluated through in vitro and in silico assays. In vitro assays demonstrated inhibition of MAO-A, MAO-B, and AChE activity in rat brain samples, suggesting potential relevance for neuroprotection. In concentration-response experiments of cerebral redox measures, thiazolidine 49 reduced lipid peroxidation, protein carbonylation, and RS levels. In radical scavenging assays, including 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH), thiazolidine 49 significantly decreased radical levels as well as exhibited ferric ion-reducing activity (FRAP assay). Additionally, no glutathione S-transferase (GST)-mimetic activity was observed. Predicted ADME/T analyses showed some aspects that may require optimization, underscoring the need for in vivo preclinical studies. Collectively, these findings support the therapeutic potential of thiazolidine 49 as an antioxidant with MAO and AChE inhibitory properties.