Abstract
Neurodegenerative ailments are a diverse set of syndromes distinguished by gradual deterioration of the structure as well as functions of the central nervous system or peripheral nervous system. Alzheimer's disease (AD) and Parkinson's disease (PD) have no cure, common, and are high prevalent neurodegenerative pathol-ogies. In current research, rationally designed thiazolidine-2,4-dione based analogs were synthesized and tested for their inhibition potential against two isoforms of monoamine oxidase (MAO-A / MAO-B). Structure activity relationships were explored. Pyridinyl and thiazolyl hydrazone derivative 43 and 44 with IC50 value of 0.013 mu M and 0.008 mu M (selectivity 228 / 226 times) exhibited higher potency than reference drug safinamide. Most active compounds showed BBB penetration in PAMPA in-vitro assay. Except nitro derivative 41, all compounds were non-neurotoxic in the studied concentration. Molecular docking studies supported the in-vitro experimental re-sults and the selectivity by comparing the binding energy values against both MAO-A and MAO-B isoforms. All the results of current research suggest compounds 43 and 44 may serve as promising candidates for further research for treatment of neurodegenerative diseases.