Filiz Bakar | Yeditepe Üniversitesi (original) (raw)

Papers by Filiz Bakar

Research paper thumbnail of Synthesis, Biological, and Computational Evaluation of Novel 1,3,5-Substituted Indolin-2-one Derivatives as Inhibitors of Src Tyrosine Kinase

Archiv der Pharmazie, 2015

Several substituted indolin-2-one derivatives were synthesized and evaluated for their activities... more Several substituted indolin-2-one derivatives were synthesized and evaluated for their activities against Src kinase. Several compounds showed activity against Src, with IC50 values in the low micromolar range. Among them, compound 2f showed the most significant activity with an IC50 value of 1.02 μM. Molecular docking studies have been performed for evaluation of the binding modes of compound 2f into the Src active site. The docking structure of compound 2f disclosed that the indole NH forms a hydrogen bond with the carbonyl of Met341. These results suggest that our novel compound 2f is a promising compound for the further development of indole-based drugs targeting Src kinase.

Research paper thumbnail of Annexin V Expression and It's Relation with Inflammatory Mediators in Colorectal Cancer Patients

Asia-Pacific Journal of Clinical Oncology

Research paper thumbnail of Effect of metformin on sex steroid levels in postmenopausal type 2 diabetic patients

Endocrine Abstracts, 2015

Research paper thumbnail of Gold Nanoparticle-Lignan Complexes Inhibited MCF-7 Cell Proliferation in vitro: A Novel Conjugation for Cancer Therapy

Anti-Cancer Agents in Medicinal Chemistry, 2015

Nanoparticles, including gold nanoparticles (AuNP), have been used in imaging in cancer treatment... more Nanoparticles, including gold nanoparticles (AuNP), have been used in imaging in cancer treatment and as therapeutic agents and drug delivery vehicles. Particularly lignans, also called phytoestrogens, have strong effects on the treatment of carcinomas due to their antiestrogenic, antiangiogenic and proapoptotic mechanism. The aim of this study is to investigate the antiproliferative effects of three lignans-AuNP conjugates, pinoresinol (PINO), lariciresinol (LARI) and secoisolariciresinol (SECO), on the MCF-7 cell lines. For this purpose, first, thiolated β -cyclodextrin (β-CD) was synthesized to achieve a surface modification of AuNP, and then the β -CD modified AuNP was characterized using the transmission electron microscopy (TEM), UV-Visible and Nuclear Magnetic Resonance (NMR) spectroscopy. Then, the selected lignans were conjugated to the β-CD-modified AuNP, and the antiproliferative effect of these conjugates was monitored. The results suggest that when compared to their non-conjugated forms, the AuNP-bound lignan conjugates prevented the proliferation of the MCF-7 cells significantly. Therefore, these AuNP-conjugated derivatives can be new candidate agents for breast cancer therapy.

Research paper thumbnail of 743: Gold nanoparticle conjugated lignan derivatives inhibited the proliferation of MCF-7 human breast cancer cells

European Journal of Cancer, 2014

Research paper thumbnail of Anti-prothrombin antibodies in type 1 diabetes mellitus

Turkish Journal of Biochemistry, 2013

Research paper thumbnail of Colchicine levels in chronic kidney diseases and kidney transplant recipients using tacrolimus

Clinical Transplantation, 2014

Tacrolimus is a CYP3A4 inhibitor and can alter colchicine metabolism. In this study, we aimed to ... more Tacrolimus is a CYP3A4 inhibitor and can alter colchicine metabolism. In this study, we aimed to evaluate plasma colchicine levels in different stages of kidney disease as well as in kidney transplant (KTx) recipients using tacrolimus. This study included six familial Mediterranean fever (FMF) patients with normal glomerular filtration rate (GFR) as controls, three patients with low GFR, six FMF patients on hemodialysis (HD), and six FMF patients who were KTx recipients using tacrolimus. After a three-d washout period, plasma colchicine levels were measured at 0 (pre-dose), one, two, four, eight, and 24 h post-dose of 1 mg oral colchicine. Area under the curve 0-24 h (AUC0-24 ) and maximum concentration (Cmax ) were evaluated and compared between the groups. Colchicine AUC0-24 was six-fold higher in HD (p < 0.001) and three-fold higher in KTx recipients (p < 0.001) when compared to the control. The low GFR group had mildly higher AUC0-24 than the control group. Cmax levels were also higher in HD (p = 0.011) and KTx recipient (p = 0.06) groups and mildly elevated in low GFR patients in comparison with controls. Colchicine AUC0-24 and Cmax were significantly increased in HD patients and KTx recipients using tacrolimus. Therefore, dose adjustments are needed to avoid toxicity in both circumstances.

Research paper thumbnail of Low-Density Lipoprotein Oxidizability and the Alteration of Its Fatty Acid Content in Renal Transplant Recipients Treated With Cyclosporine/Tacrolimus

Transplantation Proceedings, 2009

Renal transplantation is widely used to treat patients with end-stage renal disease. Atherosclero... more Renal transplantation is widely used to treat patients with end-stage renal disease. Atherosclerosis is an important posttransplantation risk factor for renal transplant recipients. Subsequent to transplantation low-density lipoprotein (LDL) particles become susceptible to oxidative modification, which results in atherosclerosis. Therefore, the aim of our study was to investigate differences in the susceptibility of LDL particles to oxidation by analyzing LDL fatty acid levels among renal transplant recipients. The changes in lag phases and fatty acid levels of LDL were observed over 4 months among renal transplant recipients treated with Cyclosporine (CsA; n ϭ 7) or Tacrolimus (FK-506; n ϭ 9). We also analyzed cholesterol and triglyceride levels of patients and healthy controls. The lag phase at the 60th day after transplantation was significantly shorter than the results either before transplantation or among control subjects. In conclusion, a similar decrease in lag phase was observed in both above groups, but the FK-506 -treated group showed a better lipid profile than the CsA-treated group.

Research paper thumbnail of Synthesis of new indole-2-carboxamide and 3-acetamide derivatives and evaluation their antioxidant properties

Journal of Enzyme Inhibition and Medicinal Chemistry, 2013

In recent years, antioxidant compounds play an important role as a health-protecting factor. Anti... more In recent years, antioxidant compounds play an important role as a health-protecting factor. Antioxidants protect cells against the damaging effects of reactive oxygen species (ROS). An imbalance between antioxidants and ROS results in oxidative stress, which leads to cellular damage and it is linked to many vital diseases. It was shown that heme oxygenase (HO) provides efficient cytoprotection against oxidative stress. In this study, a series of indole-2-carboxamide and 3-acetamide derivatives was tested for in vitro effects on HO activity and 2,2-diphenyl-1-picrylhydrazyl (DPPH) inhibition. Among the synthesized compounds, N-[3-(dimethylamino)propyl]-1H-indole-2-carboxamide 3 was found as the most activator of HO and N-(2-(dimethylamino)ethyl)-2-(1H-indol-3-yl)acetamide 8 was found the most potent inhibitor for DPPH at 10(-4) M concentration.

Research paper thumbnail of Annexin V Expression and Anti-Annexin V Antibodies in Type 1 Diabetes

The Journal of Clinical Endocrinology & Metabolism, 2014

Research paper thumbnail of Withdrawal and limitation of life support in paediatric intensive care

Archives of Disease in Childhood, 1999

Objectives-To compare the modes of death and factors leading to withdrawal or limitation of life ... more Objectives-To compare the modes of death and factors leading to withdrawal or limitation of life support in a paediatric intensive care unit (PICU) in a developing country. Methods-Retrospective analysis of all children (< 12 years) dying in the PICU (n = 148).

Research paper thumbnail of Mutations in the Gene Encoding the RER Protein FKBP65 Cause Autosomal-Recessive Osteogenesis Imperfecta

The American Journal of Human Genetics, 2010

Osteogenesis imperfecta is a clinically and genetically heterogeneous brittle bone disorder that ... more Osteogenesis imperfecta is a clinically and genetically heterogeneous brittle bone disorder that results from defects in the synthesis, structure, or posttranslational modification of type I procollagen. Dominant forms of OI result from mutations in COL1A1 or COL1A2, which encode the chains of the type I procollagen heterotrimer. The mildest form of OI typically results from diminished synthesis of structurally normal type I procollagen, whereas moderately severe to lethal forms of OI usually result from structural defects in one of the type I procollagen chains. Recessively inherited OI, usually phenotypically severe, has recently been shown to result from defects in the prolyl-3-hydroxylase complex that lead to the absence of a single 3-hydroxyproline at residue 986 of the a1(I) triple helical domain. We studied a cohort of five consanguineous Turkish families, originating from the Black Sea region of Turkey, with moderately severe recessively inherited OI and identified a novel locus for OI on chromosome 17. In these families, and in a Mexican-American family, homozygosity for mutations in FKBP10, which encodes FKBP65, a chaperone that participates in type I procollagen folding, was identified. Further, we determined that FKBP10 mutations affect type I procollagen secretion. These findings identify a previously unrecognized mechanism in the pathogenesis of OI.

Research paper thumbnail of Synthesis, Biological, and Computational Evaluation of Novel 1,3,5-Substituted Indolin-2-one Derivatives as Inhibitors of Src Tyrosine Kinase

Archiv der Pharmazie, 2015

Several substituted indolin-2-one derivatives were synthesized and evaluated for their activities... more Several substituted indolin-2-one derivatives were synthesized and evaluated for their activities against Src kinase. Several compounds showed activity against Src, with IC50 values in the low micromolar range. Among them, compound 2f showed the most significant activity with an IC50 value of 1.02 μM. Molecular docking studies have been performed for evaluation of the binding modes of compound 2f into the Src active site. The docking structure of compound 2f disclosed that the indole NH forms a hydrogen bond with the carbonyl of Met341. These results suggest that our novel compound 2f is a promising compound for the further development of indole-based drugs targeting Src kinase.

Research paper thumbnail of Annexin V Expression and It's Relation with Inflammatory Mediators in Colorectal Cancer Patients

Asia-Pacific Journal of Clinical Oncology

Research paper thumbnail of Effect of metformin on sex steroid levels in postmenopausal type 2 diabetic patients

Endocrine Abstracts, 2015

Research paper thumbnail of Gold Nanoparticle-Lignan Complexes Inhibited MCF-7 Cell Proliferation in vitro: A Novel Conjugation for Cancer Therapy

Anti-Cancer Agents in Medicinal Chemistry, 2015

Nanoparticles, including gold nanoparticles (AuNP), have been used in imaging in cancer treatment... more Nanoparticles, including gold nanoparticles (AuNP), have been used in imaging in cancer treatment and as therapeutic agents and drug delivery vehicles. Particularly lignans, also called phytoestrogens, have strong effects on the treatment of carcinomas due to their antiestrogenic, antiangiogenic and proapoptotic mechanism. The aim of this study is to investigate the antiproliferative effects of three lignans-AuNP conjugates, pinoresinol (PINO), lariciresinol (LARI) and secoisolariciresinol (SECO), on the MCF-7 cell lines. For this purpose, first, thiolated β -cyclodextrin (β-CD) was synthesized to achieve a surface modification of AuNP, and then the β -CD modified AuNP was characterized using the transmission electron microscopy (TEM), UV-Visible and Nuclear Magnetic Resonance (NMR) spectroscopy. Then, the selected lignans were conjugated to the β-CD-modified AuNP, and the antiproliferative effect of these conjugates was monitored. The results suggest that when compared to their non-conjugated forms, the AuNP-bound lignan conjugates prevented the proliferation of the MCF-7 cells significantly. Therefore, these AuNP-conjugated derivatives can be new candidate agents for breast cancer therapy.

Research paper thumbnail of 743: Gold nanoparticle conjugated lignan derivatives inhibited the proliferation of MCF-7 human breast cancer cells

European Journal of Cancer, 2014

Research paper thumbnail of Anti-prothrombin antibodies in type 1 diabetes mellitus

Turkish Journal of Biochemistry, 2013

Research paper thumbnail of Colchicine levels in chronic kidney diseases and kidney transplant recipients using tacrolimus

Clinical Transplantation, 2014

Tacrolimus is a CYP3A4 inhibitor and can alter colchicine metabolism. In this study, we aimed to ... more Tacrolimus is a CYP3A4 inhibitor and can alter colchicine metabolism. In this study, we aimed to evaluate plasma colchicine levels in different stages of kidney disease as well as in kidney transplant (KTx) recipients using tacrolimus. This study included six familial Mediterranean fever (FMF) patients with normal glomerular filtration rate (GFR) as controls, three patients with low GFR, six FMF patients on hemodialysis (HD), and six FMF patients who were KTx recipients using tacrolimus. After a three-d washout period, plasma colchicine levels were measured at 0 (pre-dose), one, two, four, eight, and 24 h post-dose of 1 mg oral colchicine. Area under the curve 0-24 h (AUC0-24 ) and maximum concentration (Cmax ) were evaluated and compared between the groups. Colchicine AUC0-24 was six-fold higher in HD (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) and three-fold higher in KTx recipients (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) when compared to the control. The low GFR group had mildly higher AUC0-24 than the control group. Cmax levels were also higher in HD (p = 0.011) and KTx recipient (p = 0.06) groups and mildly elevated in low GFR patients in comparison with controls. Colchicine AUC0-24 and Cmax were significantly increased in HD patients and KTx recipients using tacrolimus. Therefore, dose adjustments are needed to avoid toxicity in both circumstances.

Research paper thumbnail of Low-Density Lipoprotein Oxidizability and the Alteration of Its Fatty Acid Content in Renal Transplant Recipients Treated With Cyclosporine/Tacrolimus

Transplantation Proceedings, 2009

Renal transplantation is widely used to treat patients with end-stage renal disease. Atherosclero... more Renal transplantation is widely used to treat patients with end-stage renal disease. Atherosclerosis is an important posttransplantation risk factor for renal transplant recipients. Subsequent to transplantation low-density lipoprotein (LDL) particles become susceptible to oxidative modification, which results in atherosclerosis. Therefore, the aim of our study was to investigate differences in the susceptibility of LDL particles to oxidation by analyzing LDL fatty acid levels among renal transplant recipients. The changes in lag phases and fatty acid levels of LDL were observed over 4 months among renal transplant recipients treated with Cyclosporine (CsA; n ϭ 7) or Tacrolimus (FK-506; n ϭ 9). We also analyzed cholesterol and triglyceride levels of patients and healthy controls. The lag phase at the 60th day after transplantation was significantly shorter than the results either before transplantation or among control subjects. In conclusion, a similar decrease in lag phase was observed in both above groups, but the FK-506 -treated group showed a better lipid profile than the CsA-treated group.

Research paper thumbnail of Synthesis of new indole-2-carboxamide and 3-acetamide derivatives and evaluation their antioxidant properties

Journal of Enzyme Inhibition and Medicinal Chemistry, 2013

In recent years, antioxidant compounds play an important role as a health-protecting factor. Anti... more In recent years, antioxidant compounds play an important role as a health-protecting factor. Antioxidants protect cells against the damaging effects of reactive oxygen species (ROS). An imbalance between antioxidants and ROS results in oxidative stress, which leads to cellular damage and it is linked to many vital diseases. It was shown that heme oxygenase (HO) provides efficient cytoprotection against oxidative stress. In this study, a series of indole-2-carboxamide and 3-acetamide derivatives was tested for in vitro effects on HO activity and 2,2-diphenyl-1-picrylhydrazyl (DPPH) inhibition. Among the synthesized compounds, N-[3-(dimethylamino)propyl]-1H-indole-2-carboxamide 3 was found as the most activator of HO and N-(2-(dimethylamino)ethyl)-2-(1H-indol-3-yl)acetamide 8 was found the most potent inhibitor for DPPH at 10(-4) M concentration.

Research paper thumbnail of Annexin V Expression and Anti-Annexin V Antibodies in Type 1 Diabetes

The Journal of Clinical Endocrinology & Metabolism, 2014

Research paper thumbnail of Withdrawal and limitation of life support in paediatric intensive care

Archives of Disease in Childhood, 1999

Objectives-To compare the modes of death and factors leading to withdrawal or limitation of life ... more Objectives-To compare the modes of death and factors leading to withdrawal or limitation of life support in a paediatric intensive care unit (PICU) in a developing country. Methods-Retrospective analysis of all children (< 12 years) dying in the PICU (n = 148).

Research paper thumbnail of Mutations in the Gene Encoding the RER Protein FKBP65 Cause Autosomal-Recessive Osteogenesis Imperfecta

The American Journal of Human Genetics, 2010

Osteogenesis imperfecta is a clinically and genetically heterogeneous brittle bone disorder that ... more Osteogenesis imperfecta is a clinically and genetically heterogeneous brittle bone disorder that results from defects in the synthesis, structure, or posttranslational modification of type I procollagen. Dominant forms of OI result from mutations in COL1A1 or COL1A2, which encode the chains of the type I procollagen heterotrimer. The mildest form of OI typically results from diminished synthesis of structurally normal type I procollagen, whereas moderately severe to lethal forms of OI usually result from structural defects in one of the type I procollagen chains. Recessively inherited OI, usually phenotypically severe, has recently been shown to result from defects in the prolyl-3-hydroxylase complex that lead to the absence of a single 3-hydroxyproline at residue 986 of the a1(I) triple helical domain. We studied a cohort of five consanguineous Turkish families, originating from the Black Sea region of Turkey, with moderately severe recessively inherited OI and identified a novel locus for OI on chromosome 17. In these families, and in a Mexican-American family, homozygosity for mutations in FKBP10, which encodes FKBP65, a chaperone that participates in type I procollagen folding, was identified. Further, we determined that FKBP10 mutations affect type I procollagen secretion. These findings identify a previously unrecognized mechanism in the pathogenesis of OI.