Exploring 4-substituted-2-thiazolylhydrazones from 2-, 3-, and 4-acetylpyridine as selective and reversible hMAO-B inhibitors

•Synthesis and in vitro MAO inhibitory activity of new 2-thiazolylhydrazones.•hMAO-B selectivity was also corroborated by molecular modelling studies.•Thiazole substitution is important for the activity of this scaffold.•They were endowed with a reversible mechanism of enzyme inhibition.

A series of 4-substituted-2-thiazolylhydrazone derivatives have been synthesized and tested in vitro for their human monoamine oxidase (hMAO) A and B inhibitory activity. Our findings confirmed that the substitution at C4 of the thiazole ring was important to obtain highly potent and selective hMAO-B inhibitors with IC50 values in the nanomolar range. Moreover, these derivatives were endowed with a reversible mechanism of enzyme inhibition. Molecular modelling studies were performed to rationalize the recognition of all inhibitors with respect to hMAO-A and -B isoforms.

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