title: (Thiazol-2-yl)hydrazone derivatives from acetylpyridines as dual inhibitors of MAO and AChE: synthesis, biological evaluation and molecular modeling studies.
abstract: Several (thiazol-2-yl)hydrazone derivatives from 2-, 3- and 4-acetylpyridine were synthesized and tested against human monoamine oxidase (hMAO) A and B enzymes. Most of them had an inhibitory effect in the low micromolar/high nanomolar range, being derivatives of 4-acetylpyridine selective hMAO-B inhibitors also at low nanomolar concentrations. The structure-activity relationship, as confirmed by molecular modeling studies, proved that the pyridine ring linked to the hydrazonic nitrogen and the substituted aryl moiety at C4 of the thiazole conferred the inhibitory effects on hMAO enzymes. Successively, the strongest hMAO-B inhibitors were tested toward acetylcholinesterase (AChE) and the most interesting compound showed activity in the low micromolar range. Our results suggest that this scaffold could be further investigated for its potential multi-targeted role in the discovery of new drugs against the neurodegenerative diseases.
authors: a Department of Drug Chemistry and Technologies , Sapienza University of Rome , Rome , Italy .
authors: Melissa
authors: M
authors: D'Ascenzio
authors: a Department of Drug Chemistry and Technologies , Sapienza University of Rome , Rome , Italy .
authors: Paola
authors: P
authors: Chimenti
authors: b Dipartimento di Scienze della Salute , Università di Catanzaro , Catanzaro , Italy .
authors: Maria Concetta
authors: MC
authors: Gidaro
authors: a Department of Drug Chemistry and Technologies , Sapienza University of Rome , Rome , Italy .
authors: Celeste
authors: C
authors: De Monte
authors: a Department of Drug Chemistry and Technologies , Sapienza University of Rome , Rome , Italy .
authors: Daniela
authors: D
authors: De Vita
authors: a Department of Drug Chemistry and Technologies , Sapienza University of Rome , Rome , Italy .
authors: Arianna
authors: A
authors: Granese
authors: a Department of Drug Chemistry and Technologies , Sapienza University of Rome , Rome , Italy .
authors: Luigi
authors: L
authors: Scipione
authors: a Department of Drug Chemistry and Technologies , Sapienza University of Rome , Rome , Italy .
authors: Roberto
authors: R
authors: Di Santo
authors: b Dipartimento di Scienze della Salute , Università di Catanzaro , Catanzaro , Italy .
authors: Giosuè
authors: G
authors: Costa
authors: b Dipartimento di Scienze della Salute , Università di Catanzaro , Catanzaro , Italy .
authors: Stefano
authors: S
authors: Alcaro
authors: c University of Santiago de Compostela , Santiago de Compostela , Spain , and.
authors: Matilde
authors: M
authors: Yáñez
authors: d Department of Pharmacy , "G. D'Annunzio" University of Chieti-Pescara , Chieti Scalo (CH) , Italy.
authors: Simone
authors: S
authors: Carradori
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D002800:Cholinesterase Inhibitors; D006835:Hydrazones; D008996:Monoamine Oxidase Inhibitors; D011725:Pyridines; D013844:Thiazoles; D008995:Monoamine Oxidase; D000110:Acetylcholinesterase
keywords: (thiazol-2-yl)hydrazone derivatives; AChE inhibitors; Acetylpyridine; hMAO inhibitors; molecular modeling; neurodegenerative diseases