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.
Exploring (4-substituted-thiazol-2-yl)hydrazine derivatives of 2-, 3-, and 4-acetylpyridine as selective and reversible hMAO-B inhibitors / Chimenti, Paola; Petzer, A.; Carradori, S.; D’Ascenzio, M.; Silvestri, Romano; Alcaro, S.; Ortuso, F.; Petzer, J. J.; Secci, Daniela. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - 66:(2013), pp. 221-227. [10.1016/j.ejmech.2013.05.032]
Exploring (4-substituted-thiazol-2-yl)hydrazine derivatives of 2-, 3-, and 4-acetylpyridine as selective and reversible hMAO-B inhibitors.
CHIMENTI, Paola;SILVESTRI, Romano;SECCI, DANIELA
2013
Abstract
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
