Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7148
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Article Citation - WoS: 9Citation - Scopus: 8Astragalus Saponins, Astragaloside Vii and Newly Synthesized Derivatives, Induce Dendritic Cell Maturation and T Cell Activation(MDPI, 2023) Yakuboğulları, Nilgün; Çağır, Ali; Bedir, Erdal; Sağ, DuyguAstragaloside VII (AST VII), a triterpenic saponin isolated from Astragalus species, shows promise as a vaccine adjuvant, as it supported a balanced Th1/Th2 immune response in previous in vivo studies. However, the underlying mechanisms of its adjuvant activity have not been defined. Here, we investigated the impact of AST VII and its newly synthesized semi-synthetic analogs on human whole blood cells, as well as on mouse bone marrow-derived dendritic cells (BMDCs). Cells were stimulated with AST VII and its derivatives in the presence or absence of LPS or PMA/ionomycin and the secretion of cytokines and the expression of activation markers were analyzed using ELISA and flow cytometry, respectively. AST VII and its analogs increased the production of IL-1β in PMA/ionomycin-stimulated human whole blood cells. In LPS-treated mouse BMDCs, AST VII increased the production of IL-1β and IL-12, and the expression of MHC II, CD86, and CD80. In mixed leukocyte reaction, AST VII and derivatives increased the expression of the activation marker CD44 on mouse CD4+ and CD8+ T cells. In conclusion, AST VII and its derivatives strengthen pro-inflammatory responses and support dendritic cell maturation and T cell activation in vitro. Our results provide insights into the mechanisms of the adjuvant activities of AST VII and its analogs, which will be instrumental to improve their utility as a vaccine adjuvant. © 2023 by the authors.Article Citation - WoS: 15Citation - Scopus: 14Target-Driven Design of a Coumarinyl Chalcone Scaffold Based Novel Ef2 Kinase Inhibitor Suppresses Breast Cancer Growth in Vivo(American Chemical Society, 2021) Önder, Ferah Cömert; Kahraman, Nermin; Atıcı, Esen Bellur; Çağır, Ali; Kandemir, Hakan; Tatar, Gizem; Taşkın Tok, TuğbaEukaryotic elongation factor 2 kinase (eEF-2K) is an unusual alpha kinase involved in protein synthesis through phosphorylation of elongation factor 2 (EF2). eEF-2K is highly overexpressed in breast cancer, and its activity is associated with significantly shortened patient survival and proven to be a potential molecular target in breast cancer. The crystal structure of eEF-2K remains unknown, and there is no potent, safe, and effective inhibitor available for clinical applications. We designed and synthesized several generations of potential inhibitors. The effect of the inhibitors at the binding pocket of eEF-2K was analyzed after developing a 3D target model by using a domain of another a-kinase called myosin heavy-chain kinase A (MHCKA) that closely resembles eEF-2K. In silico studies showed that compounds with a coumarin-chalcone core have high predicted binding affinities for eEF-2K. Using in vitro studies in highly aggressive and invasive (MDA-MB-436, MDA-MB-231, and BT20) and noninvazive (MCF-7) breast cancer cells, we identified a lead compound that was highly effective in inhibiting eEF-2K activity at submicromolar concentrations and at inhibiting cell proliferation by induction of apoptosis with no toxicity in normal breast epithelial cells. In vivo systemic administration of the lead compound encapsulated in single lipid-based liposomal nanoparticles twice a week significantly suppressed growth of MDA-MB-231 tumors in orthotopic breast cancer models in nude mice with no observed toxicity. In conclusion, our study provides a highly potent and in vivo effective novel small-molecule eEF-2K inhibitor that may be used as a molecularly targeted therapy breast cancer or other eEF-2K-dependent tumors.Article Citation - WoS: 10Citation - Scopus: 11A New Drug Testing Platform Based on 3d Tri-Culture in Lab-On Devices(Elsevier, 2020) Gökçe, Begüm; Akçok, İsmail; Çağır, Ali; Pesen Okvur, DevrimDrug discovery has a 90% rate of failure because preclinical platforms for drug testing do not mimic the in vivo conditions. Doxorubicin (DOX) is a commonly used drug to treat breast cancer patients even though it has side effects. Lab-on-a-chip (LOC) devices provide spatial control at the micrometer scale and can thus emulate the cancer microenvironment. Here, using a multidisciplinary approach, a new drug testing platform based on 3D tri-culture in LOC devices was developed. Breast cancer cells alone or with normal mammary epithelial cells and macrophages were cultured in matrigel in LOC devices. The platform was used to test DOX and (R)-4'-methylklavuzon (KLA), which is a new anti-cancer drug candidate. Results showed that DOX and KLA were equally effective on breast cancer cells in 3D monoculture. KLA produced 26% less death for breast cancer cells than DOX in 3D tri-culture. More importantly, DOX was not selective between breast cancer cells and normal mammary epithelial cells in 3D tri- culture whereas KLA caused 56% less cell death than DOX for normal mammary epithelial cells. Results strongly recommend that 3D tri-culture in LOC devices be used for assessment of drug toxicity at the preclinical stage.Article Citation - WoS: 16Citation - Scopus: 17Antiproliferative Activity of (r)-4 '-methylklavuzon on Hepatocellular Carcinoma Cells and Epcam(+)/Cd133(+) Cancer Stem Cells Via Sirt1 and Exportin-1 (crm1) Inhibition(Elsevier Ltd., 2019) Delman, Murat; Avcı, Sanem Tercan; Akçok, İsmail; Kanbur, Tuğçe; Erdal, Esra; Çağır, AliCytotoxic effects of (R)-4'-methylklavuzon were investigated on hepatocellular carcinoma cells (HuH-7 and HepG2) and HuH-7 EpCAM(+)/CD133(+) cancer stem cells. IC50 of (R)-4'-methylklavuzon was found as 1.25 mu M for HuH-7 parental cells while it was found as 2.50 mu M for HuH-7 EpCAM(+)/CD133(+) cancer stem cells. (R)-4'-methylklavuzon tended to show more efficient in vitro cytotoxicity with its lower IC50 values on hepatocellular carcinoma cell lines compared to its lead molecule, goniothalamin and FDA-approved drugs, sorafenib and regorafenib. Cell-based Sirtuin/HDAC enzyme activity measurements revealed that endogenous Sirtuin/HDAC enzymes were reduced by 40% compared to control. SIRT1 protein levels were upregulated indicating triggered DNA repair mechanism. p53 was overexpressed in HepG2 cells. (R)-4'methylklavuzon inhibited CRM1 protein providing increased retention of p53 and RIOK2 protein in the nucleus. HuH-7 parental and EpCAM(+)/CD133(+) cancer stem cell spheroids lost intact morphology. 3D HepG2 spheroid viabilities were decreased in a correlation with upregulation in p53 protein levels. (C) 2019 Elsevier Masson SAS. All rights reserved.Article Citation - WoS: 44Citation - Scopus: 53Smart Phone Assisted Detection and Quantification of Cyanide in Drinking Water by Paper Based Sensing Platform(Elsevier Ltd., 2017) İncel, Anıl; Akın, Osman; Çağır, Ali; Yıldız, Ümit Hakan; Demir, Mustafa MuammerAn organometallic dye, europium tetrakis dibenzoylmethide triethylammonium (EuD4TEA) and gold nanoparticles (Au NPs) impregnated paper based sensor platform have been utilized for development of fluorescence turn-on cyanide assay in aqueous media. The ordinary filter paper with 6 μ m pore size were employed as solid support that facilitates impregnation of EuD4TEA and gold nanoparticles and provides durability. Detection mechanism relying on two processes (i) dissolution of gold nanoparticles causing fluorescence recovery and (ii) ligand exchange of triethyl amine with CN group stimulating cyanide specific fluorescence enhancement. The paper platform exhibit naked eye distinguishable color transition upon CN− addition from 10−2 to 10−12 M. To standardize the methodology a homemade image processing algorithm has been developed that enabling calibration of color change and quantify CN− concentration. The described algorithm is applicable to Android smart phones and facilitate transforming these devices into a quantitative cyanide detector. The overall methodology provides instrument free cyanide detection and therefore rapid control of water quality and safety at off-field conditions.Article Citation - WoS: 8Citation - Scopus: 8Synthesis and Topoisomerase I Inhibitory Properties of Klavuzon Derivatives(Elsevier Ltd., 2017) Akçok, İsmail; Mete, Derya; Şen, Ayhan; Kasaplar, Pınar; Korkmaz, Kemal S.; Çağır, AliKlavuzon is a naphthalen-1-yl substituted α,β-unsaturated δ-lactone derivative, and is one of the anti-proliferative members of this class of compounds. Asymmetric and racemic syntheses of novel α,β-unsaturated δ-lactone derivatives are important to investigate their potential for the treatment of cancer. In this study, asymmetric and racemic syntheses of heteroatom-substituted klavuzon derivatives are reported. The syntheses were completed by a well-known three-step procedure. Anti-proliferative activity of seven novel racemic klavuzon derivatives were reported against MCF-7, PC3, HCT116 p53+/+ and HCT116 p53−/− cancer cell lines. Topoisomerase I inhibitory properties of 5,6-dihydro-2H-pyran-2-one derivatives were also studied. © 2017 Elsevier Inc.Article Citation - WoS: 19Citation - Scopus: 19Synthesis of Stilbene-Fused 2'-hydroxychalcones and Flavanones(Elsevier Ltd., 2010) Akçok, İsmail; Çağır, AliSynthesis of stilbene-fused chalcones and flavanones were successfully completed. Molecules were designed in a way to mimic the structural features of both "stilbene and chalcones" or "stilbene and flavanones" at the same time, and synthesized by three steps. Heck reactions of 3-bromobenzaldehyde with styrene derivatives gave corresponding (E)-stilbenes, which were reacted with acetophenones to furnish stilbene-fused 2′-hydroxychalcones under basic conditions. Finally, intramolecular cyclization reactions were performed to produce stilbene-fused flavanones. © 2010 Elsevier Inc.Article Citation - WoS: 8Citation - Scopus: 8Michael Acceptor Properties of 6-Bicycloaryl Substituted (r)-5,6(Elsevier Ltd., 2010) Kasaplar, Pınar; Çakmak, Özgür Yılmazer; Çağır, AliThe mechanism of action for α,β-unsaturated lactones can be explained by their Michael acceptor properties. They have the potential of being covalently binding inhibitors by accepting nucleophiles from target proteins. In this work, Michael addition reactions of ethanethiol with 6-bicycloaryl substituted 5,6-dihydro-2H-pyran-2-ones were studied to explore the existence of such interactions. Three of the Michael addition products were isolated and tested over PC3 (human prostate cancer) and MCF-7 (human breast adenocarcinoma) cancer cell lines and no cytotoxicity was observed. It was revealed that biological activity depends on the existence of a Michael acceptor, but potency probably depends upon the 3D structure of the substituent on lactone ring. The primary chemical-quantum properties of the lactones were also calculated using the Spartan'08 computer program. © 2010 Elsevier Inc. All rights reserved.Article Citation - WoS: 16Citation - Scopus: 17Electrospun Amino-Functionalized Pdms as a Novel Spme Sorbent for the Speciation of Inorganic and Organometallic Arsenic Species†(Royal Society of Chemistry, 2013) Boyacı, Ezel; Horzum, Nesrin; Çağır, Ali; Demir, Mustafa Muammer; Eroğlu, Ahmet EminSol–gel based amine-functionalized SPME fibers (PDMS-weak anion exchanger) were prepared and used for direct mode extraction of dimethylarsinic acid (DMA), monomethylarsonic acid (MMA), and arsenate (As(V)) from aqueous solutions followed by HPLC-ICPMS determination. Two different methods of coating were employed: (i) electrospinning and (ii) dip coating. Electrospinning was used for the first time for preparation of sol–gel based SPME fibers and was found to be superior in terms of extracted amount of arsenicals, coating homogeneity, accessibility of amine groups on the surface, and preparation time for a single fiber. Various parameters such as solution pH, extraction time, agitation speed, extraction temperature, and ionic strength were studied. Optimum extraction conditions were determined as pH of 5.0, extraction time of 30 min, agitation speed of 700 rpm, and extraction temperature of 20 C. Extraction ability of the novel coating decreased by the addition of NaCl as a consequence of the competition between anionic arsenic species and chloride ions for active sites of the weak anion exchanger. This novel sol–gel coating prepared by electrospinning was found to be promising for SPME applications. Vibrational spectroscopy revealed the alignment of PDMS chains by elongational force under electrospinning process. The chain alignment accordingly orients the pendant amino functional groups perpendicular to the fiber surface, which may develop the free active functional groups available to the medium and lead to the enhancement of the extraction performance. Moreover, the proposed coating strategy through electrospinning might be able to break new ground for various applications in analytical chemistry as well as other disciplines.Article Citation - WoS: 50Synthesis of Aminopropyl Triethoxysilane-Functionalized Silica and Its Application in Speciation Studies of Vanadium(iv) and Vanadium(v)(Elsevier Ltd., 2011) Erdem, Aslı; Shahwan, Talal; Çağır, Ali; Eroğlu, Ahmet EminA solid phase extraction sorbent, aminopropyl triethoxysilane-functionalized silica was prepared and used for vanadium speciation prior to inductively coupled plasma mass spectrometric determination. The necessary sorption parameters such as sorption pH, reaction temperature, sorbent amount and sample volume were optimized. The sorption for V(V) and V(IV) under the optimized conditions was 98% (±1) and was lower than 10%, respectively. The sorption process was investigated both from a kinetic perspective and also in terms of Freundlich, Dubinin-Radushkevich and Langmuir isotherm models to characterize the uptake of vanadate ion by the functionalized silica. Desorption from the sorbent was realized with 0.5 mol L−1 thiourea prepared in 0.2 mol L−1 HCl. Among the possible interfering species tested, Te(IV), Se(IV), Se(VI) and Fe(III) showed interference effects with V(V) signal. The validity of the method was first checked via spike recovery experiments with four different types of water; namely ultra pure, bottled drinking, tap, and sea water for different concentrations of V(V). The percent recovery values changed between 87 and 108 for all water types. The accuracy of the proposed methodology was also checked by analyzing a standard reference material (NIST, SRM 1643e) and a good agreement was found between the determined and the certified value. The proposed methodology has also been shown to be applicable for the separate sorption of V(V) in the absence/presence of V(IV) and for the sorption of both V(IV) and V(V) in waters. The amount of V(IV) can then be determined from the difference.