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(Thiazol-2-yl)hydrazone derivatives from acetylpyridines as dual inhibitors of MAO and AChE: synthesis, biological evaluation and molecular modeling studies.
J Enzyme Inhib Med Chem. 2015 Dec; 30(6):908-19.JE

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+Show Affiliations

a Department of Drug Chemistry and Technologies , Sapienza University of Rome , Rome , Italy .a Department of Drug Chemistry and Technologies , Sapienza University of Rome , Rome , Italy .b Dipartimento di Scienze della Salute , Università di Catanzaro , Catanzaro , Italy .a Department of Drug Chemistry and Technologies , Sapienza University of Rome , Rome , Italy .a Department of Drug Chemistry and Technologies , Sapienza University of Rome , Rome , Italy .a Department of Drug Chemistry and Technologies , Sapienza University of Rome , Rome , Italy .a Department of Drug Chemistry and Technologies , Sapienza University of Rome , Rome , Italy .a Department of Drug Chemistry and Technologies , Sapienza University of Rome , Rome , Italy .b Dipartimento di Scienze della Salute , Università di Catanzaro , Catanzaro , Italy .b Dipartimento di Scienze della Salute , Università di Catanzaro , Catanzaro , Italy .c University of Santiago de Compostela , Santiago de Compostela , Spain , and.d Department of Pharmacy , "G. D'Annunzio" University of Chieti-Pescara , Chieti Scalo (CH) , Italy.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25807300

Citation

D'Ascenzio, Melissa, et al. "(Thiazol-2-yl)hydrazone Derivatives From Acetylpyridines as Dual Inhibitors of MAO and AChE: Synthesis, Biological Evaluation and Molecular Modeling Studies." Journal of Enzyme Inhibition and Medicinal Chemistry, vol. 30, no. 6, 2015, pp. 908-19.
D'Ascenzio M, Chimenti P, Gidaro MC, et al. (Thiazol-2-yl)hydrazone derivatives from acetylpyridines as dual inhibitors of MAO and AChE: synthesis, biological evaluation and molecular modeling studies. J Enzyme Inhib Med Chem. 2015;30(6):908-19.
D'Ascenzio, M., Chimenti, P., Gidaro, M. C., De Monte, C., De Vita, D., Granese, A., Scipione, L., Di Santo, R., Costa, G., Alcaro, S., Yáñez, M., & Carradori, S. (2015). (Thiazol-2-yl)hydrazone derivatives from acetylpyridines as dual inhibitors of MAO and AChE: synthesis, biological evaluation and molecular modeling studies. Journal of Enzyme Inhibition and Medicinal Chemistry, 30(6), 908-19. https://doi.org/10.3109/14756366.2014.987138
D'Ascenzio M, et al. (Thiazol-2-yl)hydrazone Derivatives From Acetylpyridines as Dual Inhibitors of MAO and AChE: Synthesis, Biological Evaluation and Molecular Modeling Studies. J Enzyme Inhib Med Chem. 2015;30(6):908-19. PubMed PMID: 25807300.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - (Thiazol-2-yl)hydrazone derivatives from acetylpyridines as dual inhibitors of MAO and AChE: synthesis, biological evaluation and molecular modeling studies. AU - D'Ascenzio,Melissa, AU - Chimenti,Paola, AU - Gidaro,Maria Concetta, AU - De Monte,Celeste, AU - De Vita,Daniela, AU - Granese,Arianna, AU - Scipione,Luigi, AU - Di Santo,Roberto, AU - Costa,Giosuè, AU - Alcaro,Stefano, AU - Yáñez,Matilde, AU - Carradori,Simone, Y1 - 2015/09/25/ PY - 2015/3/26/entrez PY - 2015/3/26/pubmed PY - 2016/6/9/medline KW - (thiazol-2-yl)hydrazone derivatives KW - AChE inhibitors KW - Acetylpyridine KW - hMAO inhibitors KW - molecular modeling KW - neurodegenerative diseases SP - 908 EP - 19 JF - Journal of enzyme inhibition and medicinal chemistry JO - J Enzyme Inhib Med Chem VL - 30 IS - 6 N2 - 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. SN - 1475-6374 UR - https://www.unboundmedicine.com/medline/citation/25807300/_Thiazol_2_yl_hydrazone_derivatives_from_acetylpyridines_as_dual_inhibitors_of_MAO_and_AChE:_synthesis_biological_evaluation_and_molecular_modeling_studies_ L2 - https://www.tandfonline.com/doi/full/10.3109/14756366.2014.987138 DB - PRIME DP - Unbound Medicine ER -