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Öğe In silico and in vitro evaluation of oxypeucedanin-induced anticancer activity: Mitotoxicity?(2023) Ergüç, Ali; Okur, Hayati; Karakuş, Fuat; Albayrak, Gökay; Arzuk, Ege; Baykan, ŞüraAim: This study aims to evaluate the alterations in Oxypeucedanin (OXY)-mediated anticancer activity in different media. Second aim is to predict the affinity of OXY to electron transfer chain (ETC) complexes. Materials and Methods: MTT and LDH leakage assays were performed with OXY. Molecular docking studies were also conducted to predict the affinity of OXY to ETC complexes. Results: 250 µM OXY reduced viability in glucose media. ≥50 µM OXY decreased viability in galactose media. ≥50 µM OXY increased membrane disruption in galactose media. Molecular docking studies also showed that OXY might possess the capacity to bind to the inhibition sites of Complex I and IV. Conclusion: Galactose-conditioned media exacerbated the OXY-mediated cytotoxicity. Preliminary results suggested that mitotoxicity might take part in anticancer activity. Furthermore, OXY might cause ETC dysfunctions due to selective inhibition of Complex I and IV.Öğe Isoimperatorin-mediated anticancer activity: Role of mitochondrial dysfunction in hepg2 cells(Ankara Üniversitesi Eczacılık Fakültesi, 2023) Ergüç, Ali; Arzuk, Ege; Albayrak, Gökay; Karakuş, Fuat; Okur, Hayati; Baykan, ŞüraObjective: The first goal of the present study is to investigate the role of mitochondria due to the Crabtree effect in HepG2 cells exposed to ISO in either glucose- or galactose-conditioned media. The second aim is to predict the interactions between electron transport chain (ETC) complexes and ISO, which might be the possible reason for mitochondrial dysfunction. Material and Method: Cell viability and membrane damage for HepG2 cells exposed to ISO (12.5, 25, 50, 100, and 250 µM) were assessed by MTT and LDH leakage assays in either glucose- or galactose-conditioned media. The affinity of ISO to ETC complexes was also determined by a molecular docking study. Result and Discussion: MTT assay showed that 250 µM ISO leads to cytotoxic activity in glucoseconditioned media, while 25 µM and higher concentrations of ISO decrease cell viability in galactose-conditioned media. A membrane damage assay conducted in a glucose-conditioned media assay revealed that 250 µM ISO disrupts the cell membrane. 100 and 250 µM ISO increased membrane damage in galactose-conditioned media. According to docking simulations, binding affinities of ISO to ETC complexes are in descending order: Complex IV > Complex I > Complex III > Complex II. Inhibition of complex IV by ISO inhibits the transfer of electrons from cytochrome c to oxygen, and the proton gradient collapses. The present study proposed that ISO leads to mitochondrial dysfunction via inhibition of the ETC.Öğe Molecular docking studies of cox inhibitors on wild-type ras(Ankara Üniversitesi Eczacılık Fakültesi, 2022) Konyar, Dilan; Okur, Hayati; Arslan, ZehraObjective: In addition to its role in the formation mechanism of inflammation, the binding potential of COX inhibitors, which can inhibit tumorogenesis by induce apoptosis, has been explored by molecular docking studies on wild-type RAS enzyme. Material and Method: KRAS enzyme (PDB ID: 4OBE), which consists is obtained by the x-ray crystallization method, was chosed considering the resolution. The 2D structures of ligand molecules were drawn in the ChemDraw 19.1. The MOE 2020 program was used to form the docking studies. Result and Discussion: As a result of docking studies, it has been understood that the presence of aromatic structures in 3a and 3b ligand molecules is critical for ligand-receptor interaction. it has been understood that there must be a certain distance between the carbonyl group and the nonpolar part of the molecule for the molecule to bind to the receptor site with a high affinity. In the following stages, more effective anticancer drug molecules can be obtained by design molecules with an appropriate diameter and length, having functional groups containing the suitable electron donor or acceptor.Öğe Oksipösedanin kaynaklı antikanser aktivitenin in siliko ve in vitro değerlendirilmesi: Mitotoksisite?(Adıyaman Üniversitesi, 2023) Ergüç, Ali; Okur, Hayati; Karakuş, Fuat; Albayrak, Gökay; Arzuk, Ege; Baykan, ŞüraAmaç: Çalışmanın amacı, farklı ortamlarda Oksipösedanin (OKS) aracılı antikanser aktivitedeki değişiklikleri değerlendirmektir. İkinci amaç, OKS’inin elektron transfer zincirine (ETZ) karşı afinitesini öngörmektir. Gereç ve Yöntem: MTT ve LDH sızma deneyleri OKS ile gerçekleştirilmiştir. Ayrıca, OKS’inin ETZ komplekslerine karşı afinitesini öngörmek için moleküler kenetlenme çalışmaları uygulanmıştır. Bulgular: Glukoz içeren ortamda 250 µM OKS canlılığı azaltmıştır. Galaktoz içeren ortamda ?50 µM OKS hücre canlılığını azalmıştır. Galaktoz içeren ortamda ?50 µM OKS membran parçalanmasını artırmıştır. Moleküler kenetlenme çalışmaları, OKS'inin Kompleks I ve IV'ün inhibisyon bölgelerine bağlanma kapasitesine sahip olabileceğini göstermektedir. Sonuç: Galaktoz içeren ortam, OKS aracılı sitotoksisiteyi artırmıştır. Ön sonuçlar, antikanser aktivitede mitotoksisitenin yer alabileceğini göstermektedir. Ayrıca OKS, Kompleks I ve IV'ün seçici inhibisyonu nedeni ile ETZ disfonksiyonuna neden olabilmektedir.Öğe Some heterocycles connected to substituted piperazine by 1,3,4-oxadiazole linker: Design, synthesis, anticholinesterase and antioxidant activity(Elsevier B.V., 2025) Kurt, Zuhal Kılıç; Konyar, Dilan; Okur, Hayati; Kaplan, Alevcan; Boǧa, MehmetAD is a multifactorial neurodegenerative disease that has caused morbidity and mortality on a global scale. Currently, there are only a few drugs used in the treatment of AD. Although many compounds that aim at new targets have reached clinical trials, none have been approved. However, discovering efficient drugs for AD treatment is one of the biggest challenges for pharmaceutical research and requires strong support. In this paper, we aim to design a series of indole, benzothiophene, and thiophene bearing 1,3,4-oxadiazole linker to the piperazine basic center and evaluate for their antioxidant and inhibitory activity against both cholinesterase enzymes. Among the compounds, 6a, 7b, and 8b exhibited moderate cationic radical scavenging activities with IC50 values ranging from 20.39 to 30.10 μM. The inhibitory activity results revealed that compounds 5c (IC50 for AChE = 53.91 μM and for BChE = 55.81 μM) and 6c (IC50 for AChE = 54.42 μM and BChE = 45.82 μM) bearing 2-fluorophenyl piperazine moiety showed both AChE and BChE inhibition with moderate IC50 values. To explore the binding properties of the target compounds into the active site of the enzyme, a molecular docking study was carried out using MOE software. The docking study showed that compound 6c targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE/BChE and formed important interactions with key residues. Moreover, theoretical physicochemical properties of the best active compound 6c were calculated by the SwissADME web service. It obeyed Lipinski's rule of five and had high GI absorption (gastrointestinal absorption) and good permeating to the blood-brain barrier (BBB). The compound 6c can be considered a promising compound and provides us directions for further research of anti-AD agent development.
