Chemistry / Kimya
Permanent URI for this collectionhttps://hdl.handle.net/11147/4072
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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.Conference Object Citation - WoS: 1Immunomodulatory Mechanisms of Astragalus Saponins(Wiley, 2021) Yakuboğulları, Nilgün; Çağır, Ali; Bedir, Erdal; Sağ, DuyguArticle 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.Editorial Citation - WoS: 8Citation - Scopus: 9Kras(g12c) Inhibitors on the Horizon(Future Science, 2019) Çağır, Ali; Azmi, Asfar S.RAS proteins (the four isoforms KRAS4A, KRAS4B, NRAS and HRAS encoded by three genes KRAS, NRAS and HRAS) act as molecular switches that when activated drive several key cellular processes such as cell growth, proliferation and survival [1]. In normal cells, RAS activity is under tight control by the precise activation (binding to GTP) and inactivation (GTP hydrolysis to GDP) [1]. As with other critical proteins, it is not at all surprising to note that the gene encoding the RAS protein isoforms is found mutated or altered in a significant proportion of tumors [2]. Mutant RAS loses its ability to hydrolyze GTP and remains in a permanently activated state (bound to GTP) leading to uncontrolled growth.Conference Object Semi-Synthetic Studies on Astragaloside Vii and Immunomodulatory Activities of the Derivatives(Georg Thieme Verlag, 2019) Yakuboğulları, Nilgün; Sağ, Duygu; Çağır, Ali; Bedir, ErdalAdjuvants have been used in vaccine sector since 1920s to increase the immunogenicity of antigens, reduce the dosage and minimize frequency of immunizations [1]. The use of saponins as adjuvant in the prophylactic/therapeutic human and veterinary vaccines, and investigation of their immunomodulatory activities have gained importance in recent years [2],[3]. Astragaloside VII (AST VII), a triterpenoid saponin isolated from Astragalus species, stimulates Th1 mediated immune response, antigen-specific antibody response and splenocyte proliferation.Article Citation - WoS: 3Citation - Scopus: 4Evaluation of Multifunctional Hybrid Analogs for Stilbenes, Chalcones and Flavanones(Bentham Science Publishers, 2017) Çağır, Ali; Odacı, Burcu; Varol, Mehmet; Akçok, İsmail; Okur, Özgür; Koparal, Ayşe T.Aims: In this study, discovery of novel anticancer agents acting by more than one mechanism was aimed. Method: For this purpose, eleven previously synthesized simple-stilbene, chalcone, flavanone derivatives and 31 novel stilbene-fused chalcones and stilbene-fused flavanones were tested for their aromatase inhibition, anti-angiogenic and anti-proliferative properties in cancer (PC3, MCF-7) and healthy (HUVEC) cell lines. MTT cell viability assay was used to evaluate the anti-proliferative activities of the compounds. CYP19/MFC high-throughput screening kit (BD Biosciences, Oxford, UK) was used to search the aromatase inhibition properties and matrigel tube formation assay was applied to determine the anti-angiogenic activities. Results: Results indicate that the simple-chalcone and flavanone derivatives were more cytotoxic than the simple-stilbenes in the both cancer cell lines. In contrast, the simple-stilbene structures were much more effective at aromatase inhibition. The cytotoxicity profiles of stilbene-fused chalcones in cancer cells imply that these molecules mostly mimic the simple chalcone structures. On the other hand, flavanones lose their cytotoxic activities after becoming fused with stilbenes. Additionally, aromatase inhibition assays showed that stilbene-fused chalcones again do mimic the simple-chalcones but not simple-stilbenes and anti-angiogenic profiles of the tested molecules seem to be not related with stilbene fragments. Furthermore, stilbene-fused flavanones may mimic both simple-flavanones and simple-stilbenes depending upon the type and position of the substituent in their respective terminal aromatic rings.Article Citation - WoS: 24Citation - Scopus: 26Composition of Carotenoids in Scenedesmus Protuberans: Application of Chromatographic and Spectroscopic Methods(Springer Verlag, 2015) Erdoğan, Ayşegül; Çağır, Ali; Conk Dalay, Meltem; Eroğlu, Ahmet EminThis study aimed to identify and determine the carotenoids from green microalga, Scenedesmus protuberans using analytical techniques. Identification of carotenoids was realized by comparing their absorption and mass spectral data with those of reference standards available and reported values. Chromatographic data were then combined with the spectroscopic information. The separation of carotenoids was achieved by C30 column and high-performance liquid chromatography-diode array detection was used for their determination. In the present work, the carotenoid content of S. protuberans was found to be 1.45 mg/g of violaxanthin, 2.47 mg/g of all-trans-lutein, 0.15 mg/g of all-trans-α-carotene, 0.55 mg/g of all-trans-β-carotene, and 0.20 mg/g of 9 or 9′-cis-β-carotene. Due to lack of their standards, the amount of all-trans-loroxanthin and cis-isomers of other carotenoids could not be quantified. In order to validate the method, Certified Reference Material (BCR 485-Mixed vegetables) was used. In conclusion, this study can serve as a reference for the analysis of carotenoids in other microalgae.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.