Guccione S

References (2)

Title : Design, synthesis and docking study of novel coumarin ligands as potential selective acetylcholinesterase inhibitors - Sonmez_2017_J.Enzyme.Inhib.Med.Chem_32_285
Author(s) : Sonmez F , Zengin Kurt B , Gazioglu I , Basile L , Dag A , Cappello V , Ginex T , Kucukislamoglu M , Guccione S
Ref : J Enzyme Inhib Med Chem , 32 :285 , 2017
Abstract : New coumaryl-thiazole derivatives with the acetamide moiety as a linker between the alkyl chains and/or the heterocycle nucleus were synthesized and in vitro tested as acetylcholinesterase (AChE) inhibitors. 2-(diethylamino)-N-(4-(2-oxo-2H-chromen-3-yl)thiazol-2-yl)acetamide (6c, IC50 value of 43 nM) was the best AChE inhibitor with a selectivity index of 4151.16 over BuChE. Kinetic study of AChE inhibition revealed that 6c was a mixed-type inhibitor. Moreover, the result of H4IIE hepatoma cell toxicity assay for 6c showed negligible cell death. Molecular docking studies were also carried out to clarify the inhibition mode of the more active compounds. Best pose of compound 6c is positioned into the active site with the coumarin ring wedged between the residues of the CAS and catalytic triad of AChE. In addition, the coumarin ring is anchored into the gorge of the enzyme by H-bond with Tyr130.
ESTHER : Sonmez_2017_J.Enzyme.Inhib.Med.Chem_32_285
PubMedSearch : Sonmez_2017_J.Enzyme.Inhib.Med.Chem_32_285
PubMedID: 28097911

Title : Potential of aryl-urea-benzofuranylthiazoles hybrids as multitasking agents in Alzheimer's disease - Kurt_2015_Eur.J.Med.Chem_102_80
Author(s) : Kurt BZ , Gazioglu I , Basile L , Sonmez F , Ginex T , Kucukislamoglu M , Guccione S
Ref : Eur Journal of Medicinal Chemistry , 102 :80 , 2015
Abstract : New benzofuranylthiazole derivatives containing the aryl-urea moiety were synthesized and evaluated in vitro as dual acetylcholinesterase (AChE)-butyrylcholinesterase (BuChE) inhibitors. In addition, the cupric reducing antioxidant capacities (CUPRAC) and ABTS cation radical scavenging abilities of the synthesized compounds were assayed. The result showed that all the synthesized compounds exhibited inhibitory activity on both AChE and BuChE with 1-(4-(5-bromobenzofuran-2-yl)thiazol-2-yl)-3-(2-fluorophenyl)urea (e25, IC50 value of 3.85 muM) and 1-(4-iodophenyl)-3-(4-(5-nitrobenzofuran-2-yl)thiazol-2-yl)urea (e38, IC50 value of 2.03 muM) as the strongest inhibitors against AChE and BuChE, respectively. Compound e38 was 8.5-fold more potent than galanthamine. The selectivity index of e25 and e38 was 2.40 and 0.37 against AChE and BuChE, respectively. Compound e2, e4 and e11 (IC50 = 0.2, 0.5 and 1.13 muM, respectively) showed a better ABTS cation radical scavenging ability than the standard quercetin (IC50 = 1.18 muM). Best poses of compounds e38 on BuChE and e25 on AChE indicate that the thiazole ring and the amidic moiety are important sites of interaction with both ChEs. In addition, the benzofuran ring and phenyl ring are anchored to the side chains of both enzymes by pi-pi(pi-pi) interactions.
ESTHER : Kurt_2015_Eur.J.Med.Chem_102_80
PubMedSearch : Kurt_2015_Eur.J.Med.Chem_102_80
PubMedID: 26244990