Kanbur, Tuğçe
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01. Izmir Institute of Technology
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2ZERO HUNGER
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3GOOD HEALTH AND WELL-BEING
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4QUALITY EDUCATION
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Scholarly Output
4
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2
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3971/1514
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1
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WoS Citation Count
24
Scopus Citation Count
26
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2
WoS Citations per Publication
6.00
Scopus Citations per Publication
6.50
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3
Supervised Theses
1
| Journal | Count |
|---|---|
| Bioorganic and Medicinal Chemistry | 1 |
| European Journal of Medicinal Chemistry | 1 |
| Journal of Thoracic Oncology | 1 |
Current Page: 1 / 1
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Now showing 1 - 4 of 4
Conference Object A Novel Inhibitor for Krasg12c Mutant Lung Carcinoma(International Association for the Study of Lung Cancer, 2020) Khan, H. Y.; Li, Y.; Aboukameel, A.; Mpilla, G.; Sexton, R.; Kanbur, Tuğçe; Nagasaka, M.; Çetinkaya, Hakkı; Çağır, AliMutations in KRAS are among the most common aberrations in cancer. However, despite considerable research efforts, KRAS remains a challenging therapeutic target. In recent years, there has been a drive to develop KRAS mutant specific drugs. Among the different known mutations, the KRASG12C (glycine 12 to cysteine) has been considered druggable. Studies have shown that due in part to the close proximity of Cysteine 12 to both the nucleotide pocket and the switch regions, thiol-reactive compounds can bind to the active site covalently and inhibit KRASG12C mutation-driven signaling. The absence of this particular cysteine residue in wild-type KRAS makes such an approach very selective towards cancer cells.Article Citation - WoS: 8Citation - Scopus: 9Crm1 Inhibitory and Antiproliferative Activities of Novel 4'-alkyl Substituted Klavuzon Derivatives(Elsevier Ltd., 2017) Kanbur, Tuğçe; Kara, Murat; Kutluer, Meltem; Şen, Ayhan; Delman, Murat; Alkan, Aylin; Otaş, Hasan Ozan; Akçok, İsmail; Çağır, AliKlavuzons are 6-(naphthalen-1-yl) substituted 5,6-dihydro-2H-pyran-2-one derivatives showing promising antiproliferative activities in variety of cancer cell lines. In this work, racemic syntheses of nine novel 4′-alkyl substituted klavuzon derivatives were completed in eight steps and anticancer properties of these compounds were evaluated. It is found that size of the substituent has dramatic effect over the potency and selectivity of the cytotoxic activity in cancerous and healthy pancreatic cell lines. The size of the substituent can also effect the CRM1 inhibitory properties of klavuzon derivatives. Strong cytotoxic activity and CRM1 inhibition can be observed only when a small substituent present at 4′-position of naphthalen-1-yl group. However, these substituents makes the molecule more cytotoxic in healthy pancreatic cells rather than cancerous pancreatic cells. Among the tested compounds 1,2,3,4-tetrahydrophenanthren-9-yl substituted lactone was the most cytotoxic compound and its antiproliferative activity was also tested in 3D spheroids generated from HuH-7 cell lines.Master Thesis Syntheses of Novel 4'-alkyl Substituted Klavuzon Derivatives(Izmir Institute of Technology, 2015) Kanbur, Tuğçe; Çağır, AliStyryl lactones, which are compounds isolated from natural sources, are known for their cytotoxic property against variety cancer cell lines. Goniothalamin is a well known member of stryl lactones, include α,β-unsaturated δ-lactone in its structure. Being a α,β-unsaturated δ-lactone subunit is an important structural feature. Since, Goniothalamin has a selective cytotoxic property for cancer cell lines with no significant cytotoxic activity toward non-malignant cells. Recent studies show that naphthalen-1-yl substituted α,β-unsaturated δ-lactone derivative has slightly better cytotoxic activity than (R)-goniothalamin. As a result of that naphthalen-1-yl substituted α,β-unsaturated δ-lactones derivative was named as klavuzon by Çağır Research group. In this study it is aimed to synthesize 4’-alkyl substituted klavuzon derivatives. Syntheses were started with the Cu catalayzed addition of Grignard reagents to ethyl 4-(bromomethyl)-1-naphthoate to achieve alkyl substitution. For lactone synthesis a well-known three steps synthesis was used starting from aldehyde. Thus 1-naphthoate esters first reduced to alcohol then oxidized to aldehyde by using LiAlH4 and PCC. These aldehydes were reacted with allymagnesium bromide then formed alcohols were acrylated with acryloyl chloride to yield the corresponding esters. Finally, target molecules were synthesised by ring closing metathesis by using 2nd generation Grubbs’ catalyst.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.