A series of new thiazole-hydrazones (3a–3n) were synthesized, characterized, and screened for their hMAOA and hMAO-B inhibitory activity by an in vitro fluorometric method. Selectivity indexes (SIs) were expressed as IC50 (MAO-A) / IC50 (MAO-B). Compound 3f showed promising hMAO-A inhibition with an IC50 value of µM and displayed a very significant SI of towards hMAO-A. The mechanism of hMAO-A inhibition was investigated by enzyme kinetics using Lineweaver–Burk graphics. Compound 3f was further screened for its cytotoxicity by using a healthy NIH/3T3 mouse embryonic fibroblast cell line (ATCC CRL1658) and was evaluated as nontoxic at its effective concentration against hMAO-A. | Turkish Journal of Chemistry Turk J Chem 2017 41 685 699 http chem ITAK c TUB Research Article doi kim-1612-78 Synthesis and MAO inhibitory activity of novel thiazole-hydrazones Ozlem ATLI1 Yusuf OZKAY 2 1 Department of Pharmaceutical Toxicology Faculty of Pharmacy Anadolu University Eski sehir Turkey 2 Department of Pharmaceutical Chemistry Faculty of Pharmacy Anadolu University Eski sehir Turkey Received Accepted Published Online Final Version Abstract A series of new thiazole-hydrazones 3a 3n were synthesized characterized and screened for their h MAO- A and h MAO-B inhibitory activity by an in vitro fluorometric method. Selectivity indexes SIs were expressed as IC 50 MAO-A IC 50 MAO-B . Compound 3f showed promising h MAO-A inhibition with an IC 50 value of µ M and displayed a very significant SI of towards h MAO-A. The mechanism of h MAO-A inhibition was investigated by enzyme kinetics using Lineweaver Burk graphics. Compound 3f was further screened for its cytotoxicity by using a healthy NIH 3T3 mouse embryonic fibroblast cell line ATCC CRL1658 and was evaluated as nontoxic at its effective concentration against h MAO-A. The ADME prediction of the compounds revealed that they may have good pharmacokinetic profiles which is necessary for drug candidates. Key words Thiazole hydrazone h MAO enzymes enzyme inhibition 1. Introduction Monoamine oxidase MAO is the key enzyme of brain function responsible for the metabolism of neurotrans- mitters by regulating the oxidative deamination of amines in neuronal glial and other cells in the brain as well as peripheral tissues. 1 4 Two main forms of this enzyme are present as MAO-A and MAO-B. MAO-A is mainly present in catecholaminergic neurons of cortex and MAO-B is found in the serotonergic neurons in the brain. 3 5 The common substrates for these enzymes are dopamine tyramine and tryptamine whereas serotonin and no- radrenaline are particularly .
