- (Thiazol-2-yl)hydrazone derivatives from acetylpyridines as dual inhibitors of MAO and AChE: Synthesis, biological evaluation and molecular modeling studies
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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.
- D'Ascenzio, Melissa,Chimenti, Paola,Gidaro, Maria Concetta,De Monte, Celeste,De Vita, Daniela,Granese, Arianna,Scipione, Luigi,Di Santo, Roberto,Costa, Giosuè,Alcaro, Stefano,Yá?ez, Matilde,Carradori, Simone
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p. 908 - 919
(2015/11/09)
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- Synthesis and biological evaluation of novel 2,4-disubstituted-1,3- thiazoles as anti-Candida spp. agents
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A new series of [4-(4′-substituted-phenyl)thiazol-2-yl]hydrazine derivatives were synthesized in good yield (86-99%) and characterized by elemental analysis, IR, 1H NMR, and mass spectral studies. The compounds were assayed for their in vitro broad-spectrum antifungal activity, compared to clotrimazole and fluconazole, against 20 clinical isolates of pathogenic Candida spp., representing five different species. The results showed that the presence of heterocyclic or bicyclic rings on hydrazone moiety in position C2 of thiazole revealed a promising selective inhibitory activity especially against Candida albicans and Candida glabrata.
- Chimenti, Franco,Bizzarri, Bruna,Bolasco, Adriana,Secci, Daniela,Chimenti, Paola,Granese, Arianna,Carradori, Simone,D'Ascenzio, Melissa,Lilli, Daniela,Rivanera, Daniela
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experimental part
p. 378 - 382
(2011/02/25)
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