Scopus İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/395
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Article Citation - Scopus: 1Possible Drug-Drug Interactions Between Mesalamine and Tricyclic Antidepressants Through CYP2D6 Metabolism - in Silico and in Vitro Analyses(Georg Thieme Verlag, 2025-04-01) Ozen, Melek B.; Gazioğlu, Işil; Ozgun-Acar, Özden; Guner, Hüseyin; Semiz, Gürkan; Sen, Alaattin; Ozgun Acar, OzdenMesalamine (mesalazine, 5-aminosalicylic acid, 5-ASA) is an essential anti-inflammatory agent both used for therapy and as a remission control in patients with inflammatory bowel diseases (IBD) such as ulcerative colitis (UC). Tricyclic antidepressants (TCAs) are used to alleviate remaining symptoms in patients already receiving IBD therapy or with quiescent inflammation. The cytochrome P4502D6 enzyme is involved in the metabolism of TCAs. Hence, it is crucial to investigate the role of CYP2D6 in 5-ASA metabolism. Initially, in silico analysis involving the docking of 5-ASA to CYP2D6 and molecular dynamics simulations was conducted. Next, the rate of O-demethylation of a nonfluorescent probe 3-[2-(N,N-diethyl-N-methylammonium)-ethyl]-7-methoxy-4-methylcoumarin (AMMC) into a fluorescent metabolite AMHC (3-[2-(N,N-diethyl-N-methylammonium)ethyl]-7-hydroxy-4-methylcoumarin) was optimized with baculosomes co-expressing human CYP2D6 and human P450 oxidoreductase (hCPR) to monitor CYP2D6 activity in a microtiter plate assay. The apparent Km and Vmax were found to be 1.30 μM and 32.68 pmol/min/mg of protein for the O-demethylation of AMMC to AMHC, and the reaction was linear for 40 min. Then, nonselective inhibition of CYP2D6 activity with various concentrations of 5-ASA was detected. Finally, the conversion of AMMC to metabolites was analyzed by HPLC-ESI-MS/MS spectrometry, and none were identified. Thus, this study suggests that concurrent use of mesalamine with TCA may lead to adverse effects, and CYP2D6 genotyping should be routinely performed on these patients to eliminate possible threats. © 2025 Elsevier B.V., All rights reserved.Article Citation - WoS: 25Citation - Scopus: 25Microwave-Assisted Green Approach for Graft Copolymerization of L-Lactic Acid Onto Starch(Wiley, 2015-10-15) Salimi, Kouroush; Topuzogullari, Murat; Dincer, Sevil; Aydin, Halil Murat; Piskin, ErhanPoly l-lactic acid grafted starch (St-g-PLA) copolymers were directly synthesized under microwave irradiation by using sodium hydroxide (NaOH) and stannous 2-ethyl hexanoate acting as a catalyst, without the use of toxic solvents. The product were characterized by Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (C-13 CP/MAS NMR), X-ray diffraction (XRD), scanning electron microscopy (SEM) and thermogravimetric analysis (TGA-DTG). SEM analysis indicated that microwave heating had a considerable effect on the interfacial adhesion between PLA and starch. Thermogravimetric analysis (TGA-DTG) revealed that copolymers exhibited better thermal stability. Maximum PLA grafting was achieved with the following reaction conditions: 450W microwave power, monomer ratio of 1:5 and 0.4M of NaOH. This study demonstrates that it is possible to obtain St-g-PLA copolymers with better processing characteristics and smaller sizes via microwave-assisted synthesis. The applied procedure is an interesting green synthesis method for the production of biodegradable materials used in a diverse range of applications. (c) 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 42937.