Person: ZENGİN KURT, BELMA
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Synthesis, antioxidant activity and SAR study of novel spiro-isatin-based Schiff bases
A new series of 21 Schiff bases of spiro-isatin was synthesized, and their DPPH, CUPRAC and ABTS cation radical scavenging abilities were investigated for antioxidant activity. The results showed that all the synthesized compounds exhibited antioxidant activity for each assay. 5 & x30d;-(2,3-Dihydroxybenzylideneamino)spiro[[1,3] dioxolane-2,3 & x30d;-indoline]-2 & x30d;-on (5c) (IC50 = 4.49 mu M, for DPPH; IC50 = 0.39 mu M, for ABTS(.+); and A(0.50) = 0.42 mu M, for CUPRAC) showed significantly better ABTS, CUPRAC and DPPH radical scavenging ability than quercetin (IC50 = 8.69 mu M, for DPPH; IC50 = 15.49 mu M, for ABTS(.+); and A(0.50) = 18.47 mu M, for CUPRAC), which is used as a standard. SAR study showed that the synthesized compounds had higher ABTS(.+) activity than DPPH and CUPRAC activities. Moreover, the compounds (5c and 5d), containing two hydroxyl groups, exhibited the highest antioxidant activities for all assays. Quantum chemical calculations were also carried out to support SAR results.
Design, synthesis and docking study of novel coumarin ligands as potential selective acetylcholinesterase inhibitors
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.
In vitro biological screening of ten edible plants from middle black sea region
Anticholinesterase, antioxidant, antiaflatoxigenic activities of ten edible wild plants from Ordu area, Turkey
Turkey has highly rich floras of medicinal and aromatic plants because of having various climate conditions in different regions. One of these regions is Middle Black Sea Region, especially Ordu Province. Extracts of 10 edible plants (Arum maculatum L., Hypericum orientale L., Ornithogalum sigmoideum Freyn et Sint., Silene vulgaris Garcke var. macrocarpa, Plantago lanceolata L., Achillea millefolium L. subsp. pannonica, Rumex crispus L., Rumex acetosella L., Capsella bursa-pastoris L., Coronopus squamatus Asch.), grown in Ordu, Turkey, were prepared with different solvents (hexane, ethanol and water, separately) and their anticholinestrase and antiaflatoxigenic activities were evaluated. Additionally, the cupric reducing antioxidant capacities (CUPRAC) and ABTS cation radical scavenging abilities of the extracts were assayed. The ethanol extract of R. acetosella exhibited the highest antioxidant activity (A0.5 value of 25.31 µg/mL, for CUPRAC activity; IC50 value of 23.73 µg/mL, for ABTS activity). The hexane extract of C. bursa-pastoris showed the strongest inhibition against AChE enzyme with IC50 value of 7.24 µg/mL, and the hexane extract of A. millefolium subsp. pannonica had the highest BChE activity with IC50 value of 6.40 µg/mL. The ethanol extract of P. lanceolata exhibited the strongest inhibition against aflatoxin with 88% inhibition.
Synthesis, anticholinesterase activity and molecular modeling study of novel carbamate-substituted thymol/carvacrol derivatives
New thymol and carvacrol derivatives with the carbamate moiety were synthesized and their inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) were evaluated. 5-isopropyl-2-methylphenyl(3-fluorophenyl)carbamate (29) was found to be the most potent AChE inhibitor with IC50 values of 2.22 mu M, and 5-isopropyl-2-methylphenyl (4-fluorophenyl)carbamate (30) exhibited the strongest inhibition against BuChE with IC50 value of 0.02 mu M. Additionally, the result of H4IIE hepatoma cell toxicity assay for compounds 18, 20, 29, 30 and 35 showed negligible cell death at 0.07-10 mu M. Moreover in order to better understand the inhibitory profiles of these molecules, molecular modeling studies were applied. Binding poses of studied compounds at the binding pockets of AChE and BuChE targets were determined. Predicted binding energies of these compounds as well as structural and dynamical profiles of molecules at the target sites were estimated using induced fit docking (IFD) algorithms and post-processing molecular dynamics (MD) simulations methods (i.e., Molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) approaches). (C) 2016 Elsevier Ltd. All rights reserved.
Antioxidant activities of novel eugenol derivatives substituted carbamate
Synthesis, Anticholinesterase, Antioxidant, and Anti-Aflatoxigenic Activity of Novel Coumarin Carbamate Derivatives
New coumarin derivatives with the carbamate moiety were synthesized and their inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) were evaluated. 4-methyl-2-oxo-2H-chromen-7-yl cycloheptylcarbamate (4h) showed the strongest inhibition against AChE with IC50 values of 2.30 mu M, and 2-oxo-2H-chromen-7-yl-(cyclohexylmethyl)carbamate (4c) and 4-methyl-2-oxo-2H-chromen-7-yl-(cyclohexylmethyl)carbamate (4g) were found to be the most potent BuChE inhibitors with IC50 value of 0.003 mu M and 0.004 mu M, respectively. Moreover antioxidant, anti-aflatoxigenic activities, protective effects against aflatoxin-B1 (AFB1) in H4IIE-C3 cells and effects on glutathione s-transferase of the synthesized compounds were investigated. The synthesized coumarin carbamates inhibited AFB1 in H4IIE-C3 cells. Western blot analyses confirmed that GST alpha protein was induced in cells treated with coumarin carbamates and AFB1. These results showed that the synthesized coumarin carbamates possess a potent protective effect against AFB1.
Synthesis and Antibacterial Activity of New Sulfonamide Derivatives Containing Thiazolidine Ring
Potential of aryl-urea-benzofuranylthiazoles hybrids as multitasking agents in Alzheimer-s disease
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-(2fluorophenyl)urea (e25, IC50 value of 3.85 mu M) and 1-(4-iodophenyl)-3-(4-(5-nitrobenzofuran-2-yl) thiazol-2-yl)urea (e38, IC50 value of 2.03 mu M) 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 ell (IC50 = 0.2, 0.5 and 1.13 mu M, respectively) showed a better ABTS cation radical scavenging ability than the standard quercetin (IC50 = 1.18 AM). 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. (C) 2015 Elsevier Masson SAS. All rights reserved.