Gazioglu I

References (7)

Title : Diurnal Changes in Capecitabine Clock-Controlled Metabolism Enzymes Are Responsible for Its Pharmacokinetics in Male Mice - Akyel_2023_J.Biol.Rhythms__7487304221148779
Author(s) : Akyel YK , Ozturk Civelek D , Ozturk Seyhan N , Gul S , Gazioglu I , Pala Kara Z , Levi F , Kavakli IH , Okyar A
Ref : J Biol Rhythms , :7487304221148779 , 2023
Abstract : The circadian timing system controls absorption, distribution, metabolism, and elimination processes of drug pharmacokinetics over a 24-h period. Exposure of target tissues to the active form of the drug and cytotoxicity display variations depending on the chronopharmacokinetics. For anticancer drugs with narrow therapeutic ranges and dose-limiting side effects, it is particularly important to know the temporal changes in pharmacokinetics. A previous study indicated that pharmacokinetic profile of capecitabine was different depending on dosing time in rat. However, it is not known how such difference is attributed with respect to diurnal rhythm. Therefore, in this study, we evaluated capecitabine-metabolizing enzymes in a diurnal rhythm-dependent manner. To this end, C57BL/6J male mice were orally treated with 500 mg/kg capecitabine at ZT1, ZT7, ZT13, or ZT19. We then determined pharmacokinetics of capecitabine and its metabolites, 5'-deoxy-5-fluorocytidine (5'DFCR), 5'-deoxy-5-fluorouridine (5'DFUR), 5-fluorouracil (5-FU), in plasma and liver. Results revealed that plasma C(max) and AUC(0-6h) (area under the plasma concentration-time curve from 0 to 6 h) values of capecitabine, 5'DFUR, and 5-FU were higher during the rest phase (ZT1 and ZT7) than the activity phase (ZT13 and ZT19) (p < 0.05). Similarly, C(max) and AUC(0-6h) values of 5'DFUR and 5-FU in liver were higher during the rest phase than activity phase (p < 0.05), while there was no significant difference in liver concentrations of capecitabine and 5'DFCR. We determined the level of the enzymes responsible for the conversion of capecitabine and its metabolites at each ZT. Results indicated the levels of carboxylesterase 1 and 2, cytidine deaminase, uridine phosphorylase 2, and dihydropyrimidine dehydrogenase (p < 0.05) are being rhythmically regulated and, in turn, attributed different pharmacokinetics profiles of capecitabine and its metabolism. This study highlights the importance of capecitabine administration time to increase the efficacy with minimum adverse effects.
ESTHER : Akyel_2023_J.Biol.Rhythms__7487304221148779
PubMedSearch : Akyel_2023_J.Biol.Rhythms__7487304221148779
PubMedID: 36762608

Title : Synthesis, anticholinesterase activity and molecular modeling study of novel carbamate-substituted thymol\/carvacrol derivatives - Kurt_2017_Bioorg.Med.Chem_25_1352
Author(s) : Kurt BZ , Gazioglu I , Dag A , Salmas RE , Kayik G , Durdagi S , Sonmez F
Ref : Bioorganic & Medicinal Chemistry , 25 :1352 , 2017
Abstract : 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 2.22muM, and 5-isopropyl-2-methylphenyl (4-fluorophenyl)carbamate (30) exhibited the strongest inhibition against BuChE with IC50 value of 0.02muM. Additionally, the result of H4IIE hepatoma cell toxicity assay for compounds 18, 20, 29, 30 and 35 showed negligible cell death at 0.07-10muM. 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).
ESTHER : Kurt_2017_Bioorg.Med.Chem_25_1352
PubMedSearch : Kurt_2017_Bioorg.Med.Chem_25_1352
PubMedID: 28089589

Title : Microwave assisted synthesis of novel hybrid tacrine-sulfonamide derivatives and investigation of their antioxidant and anticholinesterase activities - Ulus_2017_Bioorg.Chem_70_245
Author(s) : Ulus R , Zengin Kurt B , Gazioglu I , Kaya M
Ref : Bioorg Chem , 70 :245 , 2017
Abstract : A novel series of tacrine derivatives containing sulfonamide group were synthesized and their inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) were evaluated. The result showed that all the synthesized tacrine-sulfonamides (VIIIa-o) exhibited inhibitory activity on both cholinesterases. VIIIg showed the highest inhibitory activity on AChE IC50=0.009muM. This value is 220-fold greater than that of galantamine (IC50=2.054muM) and 6-fold greater than tacrine (IC50=0.055muM). VIIIf displayed the strongest inhibition of BuChE (IC50=2.250muM), which is close to donepezil (IC50=2.680muM) and 8-fold greater than that of galantamine (IC50=18.130muM) Furthermore, all of the synthesized tacrine derivatives showed higher inhibition of BuChE than that of galantamine. In addition, the cupric reducing antioxidant capacities (CUPRAC) and ABTS cation radical scavenging abilities of the synthesized compounds were investigated for the antioxidant activity. Among them, VIIIb (IC50=94.390+/-2.310muM) showed significantly better ABTS cation radical scavenging ability than all of the new synthesized compounds.
ESTHER : Ulus_2017_Bioorg.Chem_70_245
PubMedSearch : Ulus_2017_Bioorg.Chem_70_245
PubMedID: 28153340

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 : Comparison of antioxidant, anticholinesterase, and antidiabetic activities of three curcuminoids isolated from Curcuma longa L - Kalaycioglu_2017_Nat.Prod.Res__1
Author(s) : Kalaycioglu Z , Gazioglu I , Erim FB
Ref : Nat Prod Res , :1 , 2017
Abstract : Antioxidant, anticholinesterase and antidiabetic activities of three curcuminoids isolated from the Curcuma longa were simultaneously tested and compared in this study. The highest antioxidant power was detected for curcumin with the applied methods. The drug potentials of curcuminoids for Alzheimer's disease were controlled. Bisdemethoxycurcumin (BDMC) showed substantial inhibitory activity. The activity of demethoxycurcumin (DMC) followed BDMC, whereas curcumin showed very little acetylcholinesterase inhibition activity. Antidiabetic activity of curcuminoids was evaluated by their alpha-glucosidase inhibitory activities. All curcuminoids show activities with decreasing order as BDMC > curcumin > DMC. The significant activities of BDMC compared to its isomers and examination of chemical structures of isomers might be a starting point in designing new drugs for Alzheimer's and Diabetes Mellitus.
ESTHER : Kalaycioglu_2017_Nat.Prod.Res__1
PubMedSearch : Kalaycioglu_2017_Nat.Prod.Res__1
PubMedID: 28287280

Title : Synthesis, antioxidant and anticholinesterase activities of novel coumarylthiazole derivatives - Kurt_2015_Bioorg.Chem_59C_80
Author(s) : Kurt BZ , Gazioglu I , Sonmez F , Kucukislamoglu M
Ref : Bioorg Chem , 59C :80 , 2015
Abstract : A newly series of coumarylthiazole derivatives containing aryl urea/thiourea groups were synthesized and their inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BCHE) were evaluated. The result showed that all the synthesized compounds exhibited inhibitory activity to both cholinesterases. Among them, 1-(4-(8-methoxy-2-oxo-2H-chromen-3-yl)thiazol-2-yl)-3-(4-chlorophenyl)thiourea (f8, IC50=4.58muM) was found to be the most active compound against AChE, and 1-(4-fluorophenyl)-3-(4-(6-nitro-2-oxo-2H-chromen-3-yl)thiazol-2-yl)urea (e31) exhibited the strongest inhibition against BCHE with IC50 value of 4.93muM, which was 3.5-fold more potent than that of galantamine. The selectivity of f8 and e31 were 2.64 and 0.04, respectively. In addition, the cupric reducing antioxidant capacities (CUPRAC) and ABTS cation radical scavenging abilities of the synthesized compounds were investigated for antioxidant activity. Among them, f8, f4 and f6 (IC50=1.64, 1.82 and 2.69muM, respectively) showed significantly better ABTS cation radical scavenging ability than standard quercetin (IC50=15.49muM).
ESTHER : Kurt_2015_Bioorg.Chem_59C_80
PubMedSearch : Kurt_2015_Bioorg.Chem_59C_80
PubMedID: 25706320

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