Chemistry / Kimya
Permanent URI for this collectionhttps://hdl.handle.net/11147/4072
Browse
3 results
Search Results
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: 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.