64038-88-6Relevant articles and documents
Design, synthesis and biological assessment of new thiazolylhydrazine derivatives as selective and reversible hMAO-A inhibitors
Can, Nafiz ?ncü,Osmaniye, Derya,Levent, Serkan,Sa?l?k, Begüm Nurpelin,Korkut, Bü?ra,Atl?, ?zlem,?zkay, Yusuf,Kaplanc?kl?, Zafer As?m
, p. 68 - 81 (2017/12/26)
In the recent works, it was shown that numerous thiazolylhydrazine derivatives display hMAO inhibitory activity in the range of micromolar concentration. Hence, in the present study a new series of new thiazole-hydrazines (3a-3n) were designed, synthesized, characterized and screened for their hMAO-A and hMAO-B inhibitory activity by an in vitro flurometric method. The enzyme inhibition assay revealed that most of the synthesized compounds have selective inhibition potency against hMAO-A. The compounds 3f and 3h showed promising hMAO-A inhibition with an IC50 values of 0.012 μM and 0.011 μM and significant selectivity indexes of 1214 and 1601 towards hMAO-A, respectively. The mechanism of hMAO-A inhibition of compounds 3f and 3h was investigated by Lineweaver-Burk graphics and reversible-competitive inhibition of hMAO-A was determined. Cytotoxicity and genotoxicity studies were carried out and the compound 3h was found as non-cytotoxic and non-genotoxic. Theoretical calculation of ADME properties suggested that synthesized compounds may have a good pharmacokinetic profile. The docking study of compound 3f and 3h revealed that there is a strong interaction between the active sites of hMAO-A and analyzed compound.