Sürdürülebilir Kalkınma Amaçları
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- ArticleAçık Erişim2022In Vitro Cytotoxic Evaluation of a Silver(I) Complex Including Non-Steroidal Anti-Inflammatory Drug Niflumic Acid and 3-Picoline on Human-Derived Cancer Cell Lines
Caglar, Bulent; Altay, Ahmet; Yeniçeri, Esma Kübra Kağan; Caglar, Sema; Harurluoğlu, Betül
Burada, steroidal olmayan anti-enflamatuar ilaç niflumik asit ve 3-pikolin içeren yeni bir gümüş(I) kompleksi sentezlendi ve FT-IR, 1H NMR, elemental ve termik analiz teknikleri ile karakterize edildi. Bu teknikler, sentezlenen kompleksin formülünün [Ag(nif)(3-pic)] olduğunu gösterdi. Kompleks, ligand (niflumik asit) ve gümüş iyonlarının tek başına sitotoksik yeteneği, insan meme adenokarsinomu (MDA-MB-453), akciğer adenokarsinomu (A-549), kolorektal adenokarsinom (HT-29) ve fare fibroblast hücre hatlarına (3T3-L1) karşı test edildi. XTT sonuçları, AgNO3 ve niflumik asidin tek başına kanser ve sağlıklı hücre hatları üzerinde orta düzeyde sitotoksisite sergilemesine rağmen, kompleksin kanser hücreleri üzerinde doza bağlı bir şekilde güçlü sitotoksik aktivite gösterdiğini gösterdi. Kompleksin en güçlü sitotoksisitesi ve en yüksek seçiciliği HT-29 hücrelerinde belirlendi. Bu bulgular, gelişmiş antikanser çalışmalarında yeni gümüş(I) kompleksinin değerlendirilmesi için temel çıktılar sağlar.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2022Diffractaic acid, a novel TrxR1 inhibitor, induces cytotoxicity, apoptosis, and antimigration in human breast cancer cells
Kalın, Şeyda Nur; Altay, Ahmet; Budak, Harun
Breast cancer represents one of the most frequently encountered cancer types among women worldwide. Thioredoxin reductase 1 (TrxR1) is a therapeutic target for breast cancer therapy due to its overexpression in tumor cells. The current research aims to determine the anticancer effect of diffractaic acid, a lichen acid, in breast cancer, and research whether the anticancer effect of diffractaic acid occurs through TrxR1 targeting. According to the XTT assay results, diffractaic acid induced cytotoxicity in both MCF-7 and MDA-MB-453 cells with IC50 values of 51.32 μg/ml and 87.03 μg/ml, respectively. Flow cytometry and cell migration analyses revealed the apoptotic, necrotic, and antimigratory effects of diffractaic acid. qPCR analysis indicated the upregulation of the BAX/BCL2 ratio and the P53 gene in MCF-7 cells with only the P53 gene in MDA-MB-453 cells. The gene, protein, and enzyme activity of TrxR1 were suppressed in MCF-7 cells, whereas only enzyme activity was suppressed in MDA-MB-453 cells. These findings illustrate the anticancer effect of diffractaic acid on breast cancer targeting TrxR1. In conclusion, these data reveal that diffractaic acid may be considered an effective therapeutic agent for breast cancer treatment.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2022Phytochemical Analysis and Biological Evaluation of Hypericum linarioides Bosse: in Vitro and in Silico Studies
Altay, Ahmet; Yeniçeri, Esma Kübra Kağan; Taslimi, Parham; Taskin-Tok, Tugba; Yılmaz, Mustafa Abdullah; Köksal, Ekrem
The aim of this study is to determine the phenolic composition of Hypericum linarioides Bosse, to assess its various biological properties, and finally to confirm the experimental data of enzyme inhibitions via docking studies. LC-MS/MS analysis performed over methanol extract (ME) revealed the presence of 27 phytochemicals. Antioxidant activity results indicated that ME had the strongest DPPH radical scavenging and ferric ion reducing capacity than water and hexane extracts. XTT assays revealed the strongest anti-proliferative activity of ME against MCF-7 and HT-29 cancer cells. Flow cytometry results also confirmed the notable apoptotic effect of ME on MCF-7 cells through mitochondria-dependent pathway. Enzyme activity results exhibited the most promising acetylcholinesterase and α-glycosidase inhibitory activities of the ME. Molecular docking calculations of α-glycosidase with the major compounds (1, 15, 17 and 19) indicated that 17 (isoquercitrin) had the best docking binding energy (−10.92 kcal/mol) with appropriate binding interactions.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2022Synthesis, structural characterization and evaluation of anticancer activity of polymeric silver(I) complexes based on niflumic acid/naproxen and picoline derivatives
Caglar, Sema; Altay, Ahmet; Harurluoglu, Betul; Yeniceri, Esma K. K.; Caglar, Bulent; Şahin, Onur
Two polymeric mixed-ligand silver(I) complexes, [Ag(µ-nif)(4-pic)]n (1) and [Ag4(µ-nap)4(2-pic)2]n (2), where Hnif: niflumic acid, Hnap: naproxen, 4-pic: 4-picoline and 2-pic: 2-picoline, were synthesized and characterized by single-crystal X-ray diffraction, FT-IR and 1H NMR spectroscopies, elemental and thermal analysis techniques. In 1, nif ligand behaves as a µ3-N,O,O' bridge connecting three silver(I) ions and each silver(I) ion exhibits a seesaw geometry. In 2, nap ligands act as a µ-carboxylato-(O,O') bridge between two silver(I) ions and µ3-carboxylato-(O,O,O') bridge linking three silver(I) ions. Each silver(I) ion occurs in trigonal geometry. To uncover the anticancer properties of the complexes, first, their cytotoxic abilities were tested against three cancer cell lines, HT-29 (human colorectal adenocarcinoma), A-549 (human lung carcinoma), and MDA-MB-453 (human breast adenocarcinoma), and normal 3T3-L1 (mouse fibroblast) cell line by XTT tests. Afterwards, the anticancer mechanism of the complexes was tried to be elucidated through the flow cytometry analyzes. XTT assay results showed that the complexes exhibited the highest cytotoxic activity and selectivity on HT-29 cells among all the cell lines. Flow cytometry analyses revealed that both complexes induced the apoptosis through the mitochondrial membrane depolarization and activation of the caspase cascade in HT-29 cells.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2022A bis indole analog molecule fluorescent probe for living cell staining
Beşer, Burcu Meryem; Altay, Ahmet; Talaz, Oktay; Türkmenoğlu, Burçin
In this study, the fluorescent probe property of a bis indole compound (5,14-dimethyl-5,6,7,8,9,14-hexahydroindolo [2 ', 3′: 3,4] cycloocta [1,2-b] indole), a Caulerpin derivative, which is a member of the indole family, was investigated. For this purpose, firstly, the fluorescence character of the molecule was investigated by absorption and fluorescence spectroscopy techniques in both solvent and surfactant environments. Afterwards, the cytotoxicity of the molecule was tested on the human colon cancer HT-29 cells and breast cancer MCF-7 cells as well as mouse fibroblast 3T3-L1 cells. After determining that the molecule has no cytotoxic effect against all the tested cell lines by 100 µM, the cell staining feature of the probe was examined. The obtained data showed us that the molecule, whose confocal microscopy images were taken at 360 nm excitation wavelength, stained the cell cytoplasm. In addition, optical absorption spectra, oscillator strength (f), transition configuration and transition characteristics of the Ars-In in different solvents were investigated at the theoretical level using Time Dependent-Density Functional Theory (TD-DFT). In conclusion, these results confirm that this indole derivative molecule could be evaluated as an effective fluorescence probe for biological systems.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2022Fluorescence interactions of a novel chalcone derivative with membrane model systems and human serum albumin
Yildirim, Berat; Beşer, Burcu Meryem; Çolak, Nevin Ulaş; Altay, Ahmet; Yaşar, Ahmet
A novel chalcone derivative (4-(5-(pyridin-2-yl)-4,5-dihydro-1H-pyrazol-3-yl) phenol (PDP) was synthesized, characterized and investigated for its potential as a fluorescent probe. The structure of the synthesized molecule was determined by FTIR, 1H NMR, 13C NMR and LC-MS/MS. The interactions of PDP with fluorescent dyes in aqueous SDS environment and HSA were studied by using fluorescence resonance energy transfer (FRET) technique and steady-state and time-resolved fluorescence spectroscopy techniques. In addition, the cytotoxic effects of PDP against various cell lines (MCF -7, HT −29, and 3 T3-L1) as well as their corresponding healthy cell lines were tested by MTT assay and visualization of FRET efficiency of PDP in vitro was monitored by confocal microscopy. MTT assay showed that PDP has no significant cytotoxic effect on HT −29 cancer cells and moderate cytotoxicity on MCF -7 and 3 T3-L1 cells even at a concentration of 250 μM. Combining confocal microscopes with the FRET technique showed that PDP significantly stained the cytoplasm of MCF -7 cell lines. These results suggest that PDP could be used in fluorescence microscopy for cell staining.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2022Inhibition of thioredoxin reductase 1 by vulpinic acid suppresses the proliferation and migration of human breast carcinoma
Kalın, Şeyda Nur; Altay, Ahmet; Budak, Harun
Aims: It was aimed to investigate the thioredoxin reductase 1 (TrxR1)-targeted anticancer effect of vulpinic (VA) and lecanoric (LA) acids, which are lichen secondary metabolites, on breast cancer MCF-7 and MDA-MB-453 cell lines, and to compare the effectiveness of this potential effect against commercial chemotherapeutic drugs carboplatin and docetaxel. Main methods: The anticancer effects of both lichen metabolites were evaluated by XTT, flow cytometry analysis, cell scratch, and transwell migration assays. Apoptotic results were also confirmed by qPCR and western blot. Changes in TrxR1 were investigated in gene and protein expressions and enzyme activity levels. Key findings: VA suppressed the proliferation of MCF-7 and MDA-MB-453 cells in a dose- and time-dependent manner, and the IC50 values were calculated as 22.92 μg/ml and 95.65 μg/ml, respectively. As for LA, it did not have a considerable antiproliferative effect on both cell lines. VA had stronger cytotoxicity than both chemotherapeutic drug in MCF-7 cells and showed antiproliferative activity closer to carboplatin in MDA-MB-453 cells. qPCR, western blot, and flow cytometry analysis results revealed that VA did not induce apoptosis in both cell lines. In contrast, VA caused cell cycle arrest, significantly. Migration assay results showed that VA suppressed migration in both cells. VA induced the gene expression of TrxR1 while inhibiting its protein expression and enzymatic activity in both cell lines. Significance: The findings reveal that vulpinic acid may be a novel inhibitor candidate on TrxR1 and could be considered a potential chemotherapeutic agent for breast cancer treatment, especially in MCF-7 cells.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2022LC-MS/MS analysis and diverse biological activities of Hypericum scabrum L.: In vitro and in silico research
Altay, Ahmet; Yeniceri, Esma; Taslimi, Parham; Taskin-Tok, Tugba; Yilmaz, Mustafa Abdullah; Koksal, Ekrem
This study was designed to determine the phytochemical composition of Hypericum scabrum extracts and investigate their biologically prominent activities. LC-MS/MS analysis revealed the presence of 29 phytochemicals in the plant extracts. The methanol extract (ME) exhibited the strongest DPPH radical scavenging (IC50: 18.57 µg/mL) and ferric ion reducing capacity (74.20 mg TEAC/g). Besides, ME displayed the most promising α-glycosidase (IC50: 1.88 µg/mL) and acetylcholinesterase AChE (IC50: 8.41 µg/mL) inhibitory effect. The XTT assay results displayed the strong anti-proliferative activity of ME against MCF-7 (IC50: 56.45 µg/mL) and MDA-MB-453 (IC50: 67.79 µg/mL) cell lines. Flow cytometry studies confirmed the mitochondrial-dependent apoptotic effect of ME in MCF-7 cells. Finally, molecular docking studies revealed the best binding affinity of the compounds 1, 9, and 41 with AChE and α-Gly, while 41 exhibited the best affinity against caspase-3, caspase-9 and DNA. To conclude, this study provides essential data for further in vivo studies.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2022Design, synthesis, anticancer evaluation and molecular docking studies of new imidazo [2, 1-b] thiazole -based chalcones
Dadou, Said; Altay, Ahmet; Koudad, Mohammed; Türkmenoğlu, Burçin; Yeniçeri, Esma; Çağlar, Sema; Allali, Mustapha; Oussaid, Adyl; Benchat, Noureddine; Karrouchi, Khalid
A new series of imidazo[2, 1-b]thiazole-based chalcone derivatives were designed, synthesized, and tested for their anticancer activities. Firstly, the cytotoxic ability of the compounds was tested on three different types of cancer cells, namely colorectal adenocarcinoma (HT-29), lung carcinoma (A-549), breast adenocarcinoma (MCF-7), and mouse fibroblast cells (3T3-L1) by XTT tests. Afterwards, further anticancer activity studies with the compound 3j having the lowest IC50 and highest SI values were performed on MCF-7 cells. XTT results revealed that all the test compounds exhibited much higher cytotoxic activity on the cancer cells than that of normal 3T3-L1 cells. Among the compounds, 3j especially stood out with its IC50 (9.76 µM) and SI (14.99) values on MCF-7 cells. Flow cytometry analysis proved that 3j-treated MCF-7 cells was resulted in the mitochondrial membrane depolarization, multicaspase activation, and ultimately apoptosis. Additionally, in silico molecular docking approaches were carried out to confirm the experimental observations and investigate the efficacy of the compound 3j. The interactions of 3j on DNA dodecamer and caspase-3 were investigated by molecular docking studies. Based on these interactions, the active amino acids in the binding site were determined and their free binding energies (ΔGBind) were calculated.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2022Silver(I) complexes containing diclofenac and niflumic acid induce apoptosis in human-derived cancer cell lines
Altay, Ahmet; Caglar, Sema; Caglar, Bulent
We investigated the anti-cancer activity of [Ag(μ-dicl)] n 1 and [AgH(nif)2] 2 complexes against human cancer cell lines (MCF-7, HT-29, and HepG2) and mouse fibroblast (3T3-L1) cell line. Anti-proliferative activity was monitored by XTT cell viability and LDH leakage assays. Cell death mode was evaluated by multi-caspase activity, annexin V cytofluorimetric, MMP, cell cycle arrest, and ROS generation assays. Antioxidant capacity was evaluated on SOD, GPx, GR, and CAT enzymes. The XTT and LDH assay results showed that both complexes exhibited strong cytotoxicity against the tested cancer cell lines. The apoptotic mechanisms of the complexes were demonstrated by loss of MMP and increase in phosphatidylserine translocation, sub-G1 phase, and multi-caspase activity. Besides, both complexes induced the oxidative stress in MCF-7 cells by decreasing the activity of GPx, GR, and CAT enzymes. In conclusion, both Ag(I) complexes, especially 1, warrant for further in vivo evaluation as a new alternative in cancer treatment.Highlights Ag(I) complexes inhibited cell proliferation and induced LDH leakage in human cancer cell lines. Ag(I) complexes induced apoptosis through MMP disruption and ROS generation. Ag(I) complexes mimicked the multi-caspase activity. Ag(I) complexes increased the accumulation of sub-G1 phase. Ag(I) complexes inhibited the activity of antioxidant system enzymes.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2022A Biochemical Approach for Hedysarum candidissimum from Turkey: Screening Phytochemicals, Evaluation of Biological Activites, and Molecular Docking Study
Altay, Ahmet; Yeniceri, Esma; Taslimi, Parham; Taskin-Tok, Tugba; Yilmaz, Mustafa Abdullah; Koksal, Ekrem
This study was designed to screen the phytochemical composition and investigate the biological activities of Hedysarum candidissimum extracts and also support the results with molecular docking studies. LC/MS/MS analysis revealed the presence of 22 phytochemical constituents (mainly phenolic acids, flavonoids, and flavonoid glycosides) in the plant structure. The methanol extract exhibited the strongest antioxidant activity among all the extracts with its strong DPPH radical scavenging and iron reducing capacity, as well as high phenolic and flavonoid contents. Additionally, it was found to be the most promising acetylcholinesterase (AChE: IC50: 93.26 μg/mL) and α-glycosidase (AG: IC50: 28.57 μg/mL) inhibitory activities, supported by the major phenolics of the species through in silico studies. Ethyl acetate extract had the strongest cytotoxic effect on HT-29 (IC50: 63.03 μg/mL) and MDA-MB-453 (IC50: 95.36 μg/mL) cancer cell lines. Both extracts exhibited considerable apoptotic and anti-migrative effects on HT-29 cells. The investigations provide phyto-analytical and bio-pharmacological results which can be extended by in vivo studies in the future.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2021Lallemantia canescens (L) Fisch & Mey. Bitkisinin Antimikrobiyal Aktivitesinin Araştırılması
Akyüz, Sümeyye; Köksal, Ekrem; Altay, Ahmet; Alp, Cemalettin; Altin, Sevgi; Yeniçeri, Esma Kübra Kağan
Bitkilerin zararlı mikroorganizmaları öldürücü etkileri ile ilgili yapılan çalışmalar onların sağlık açısından önemli ve değerli bir kaynak haline gelmelerini sağlamıştır. Türkiye üç fitocoğrafik bölgenin birleşim merkezi olmasından dolayı zengin florasıyla sayısız tıbbi ve aromatik bitkiye ev sahipliği yapmaktadır. Bu çalışmada Türkiye’de “Topajdarbaşı” olarak bilinen L. canescens bitkisinin toprak üstü kısımlarının hekzan, etilasetat, metanol ve su ekstrelerinin antimikrobiyal aktivitesi araştırılmıştır. Bitki örnekleri Erzincan İli Pöske Dağı bölgesinden toplanmıştır. Ekstraktların antimikrobiyal aktiviteleri; standart Gram negatif bakterilere (Pseudomonas aeruginosa, Klebsiella pneumoniae, kolistin dirençli Escherichia coli, Escherichia coli) ve standart Gram pozitif bakterilere (Enterococcus faecalis, Staphylococcus aureus, Streptococcus pneumoniae) karşı Kirby-Bauer disk difüzyon yöntemi ile belirlenmiştir. L. Canescens’in hekzan, etilasetat ve metanol ekstreleri S. aureus, E. faecalis, S. pneumoniae suşlarına karşı antimikrobiyal aktivite göstermiştir.
RDL Kalıcı Kaydıİncele - Proje2021Liken Asitlerinin İnsan Akciğer ve Karaciğer Kanser Hücre Hatları Üzerine Tiyoredoksin Redüktaz Hedefli Antikanser Etkisinin Gen ve Protein Seviyesinde Araştırılması
Altay, Ahmet; Budak, Harun
Kanser, kardiyovasküler hastalıklardan sonra en sık görülen ikinci ölüm nedenidir. Kanserden kaynaklı ölüm oranlarının daha yüksek olması, bilim insanlarının ve kuruluşların bu konuya daha fazla ilgi göstermesine yol açmıştır. DNA sentezi/onarımı, anjiyogenez gibi birçok hücresel olayda hayati fonksiyonlara sahip olan Tiyoredoksin Redüktaz (TRXR), akciğer ve karaciğer gibi birçok agresif tümör tipinde aşırı derecede eksprese edildiği için, kanser çalışmalarında seçici bir markır olarak kullanılır. 2018 yılında yayımlanan çalışmamızda, bazı liken asitlerinin (difraktaik, evernik, lobarik, lekanorik ve vulpinik asit) sıçan akciğerinden saflaştırılan TRXR enzimi üzerine inhibe edici etkisinin ticari antikanser ilaçları olan sisplatin ve doksorubisinden daha güçlü olduğu gösterilmiştir. Literatürde, insan akciğer (A549) ve karaciğer (HepG2) kanseri hücrelerinde belirtilen liken asitlerinin tiyoredoksin redüktaz hedefli antikanser etkisinin araştırıldığı çalışmaların bulunmaması projeyi özgün kılmaktadır. Bu projenin amacı, yukarıda belirtilen liken asitlerinin A549 ve HepG2 kanser hücreleri üzerindeki antikanser etkisini detaylı şekilde araştırmak ve bu etkinin TRXR1 aracılığıyla olup olmadığını hem moleküler hem de protein seviyelerinde incelemektir. Farklı konsantrasyonlarda liken asitleri muamelesiyle A549 ve HepG2 kanser hücrelerinde hücre proliferasyon testi yapıldı. Etkin IC50 konsantrasyonu ve uygulama süresi belirlendikten sonra bu liken asitlerinin apoptoz ve migrasyon üzerine, apoptotik yolak genleri olan BAX, BCL-2 ve P53?ün kantitatif ekspresyonu üzerine etkileri her iki kanser hücre hattında incelendi. Ayrıca, her iki kanser hücre hattının liken asitleriye inkübasyonu durumunda TRXR1'nin kantitatif gen ve protein ekspresyonlarına ve TRXR1 enziminin spesifik aktivitesi üzerine etkisine bakıldı. Difraktaik, evernik, lobarik ve vulpinik asit her iki hücre hattında da antiproliferatif etki gösterdi ve apoptozu indükledi. Lekanorik asit iki hücre hattında da antikanser etki göstermedi. TRXR1?in aktivitesini A549 hücresinde difraktaik asit baskılarken HepG2 hücresinde ise difraktaik ve vulpinik asitleri baskıladı. Sonuç olarak, difraktaik ve vulpinik asitleri TRXR1 hedefli antikanser özellik gösterdi.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2021In vitro Antioxidant and Cytotoxic Activities of Extracts of Endemic Tanacetum erzincanense Together with Phenolic Content by LC-ESI-QTOF-MS
Yapıcı, İsmail; Altay, Ahmet; Öztürk Sarıkaya, Beyza; Korkmaz, Mustafa; Atila, Alptuğ; Gülçin, İlhami; Köksal, Ekrem
In this study, phenolic composition, and in vitro biological activities of ethyl acetate (EAE) and methanol (ME) extracts obtained from the aerial parts of endemic Tanacetum erzincanense were investigated. Total phenolic and flavonoid content of the extracts were determined by Folin-Ciocalteu and aluminum chloride colorimetric methods, respectively. Antioxidant capacity of the extracts was evaluated over radical scavenging (DPPH and ABTS) and metal ion reducing power (FRAP and CUPRAC) tests. Individual phenolic compounds in ME was analyzed by high-performance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF/MS). Cell inhibitory potential of the extracts was tested against colorectal adenocarcinoma (HT-29), breast adenocarcinoma (MCF-7), and hepatocarcinoma (HepG2) cells by 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay. The results showed that ME contains higher TPC (64.4 mg GAE/g) and TFC (62.2 mg QE/g) than those of EAE (41.5 mg GAE/g and 40.0 mg QE/g). LC-ESI-QTOF/MS analysis revealed that ME is rich in phenolic compounds, namely, chlorogenic acid, apigenin, quercetin, luteolin, and diosmetin. Antioxidant assay results indicated that ME possess stronger activity than EAE and a power that competes with synthetic antioxidants. XTT assay results demonstrated that although both extracts displayed a considerable cytotoxicity against the tested cancer cell lines in a time and dose-dependent manner, ME expressed its selective inhibitory action towards MCF-7 cells with an IC50 value of 20.4 μg/mL for 72 h. These results may serve as a basis for further in vivo studies to examine the potential applications of T. erzincanense in food and pharmaceutical industries.
RDL Kalıcı Kaydıİncele - ArticleYayıncıda açık erişim2021In Vitro Anticancer Activity of Novel Co(II) and Ni(II) Complexes of Non-steroidal Anti-inflammatory Drug Niflumic Acid Against Human Breast Adenocarcinoma MCF-7 Cells
Caglar, Sema; Altay, Ahmet; Kuzucu, Mehmet; Caglar, Bulent
Herein, we report the synthesis, characterization and anticancer activity of six novel complexes of non-steroidal anti-inflammatory drug niflumic acid with Co(II) and Ni(II). In vitro cytotoxicity screening in MCF-7, HepG2 and HT-29 cancer cell lines showed that the complex 3 [Co(nif)2(met)(4-pic)] and complex 6 [Ni(nif)2(met)(4-pic)] among all the complexes exhibited the highest cytotoxicity against MCF-7 cells with IC50 values of 11.14 µM and, 41.47 µM, respectively. Besides, all the complexes exhibited significantly higher selectivity towards mouse fibroblast 3T3L1 cells. Further mechanistic studies with both complexes on MCF-7 cells revealed their cytotoxic action through the mitochondrial-dependent apoptotic pathway causing an increase oxidative/nitrosative stress, decrease in mitochondrial membrane potential (ΔΨm), inducing the multicaspase activation and arresting the cell cycle at S phase. q-PCR analysis resulted in an increase in the expression of the apoptotic marker proteins bax, p53 and caspase-3 and -8 in MCF-7 cells, but a decrease in the expression of antiapoptotic bcl-2 gene. Moreover, both complexes induced the apoptosis through the inhibition of PI3K/Akt signaling pathway by decreasing the expression of PI3K and increasing dephosphorylation form of Akt protein. These results provide a significant contribution to the explanation of the anticancer mechanisms of these complexes in MCF-7 cells. [Figure not available: see fulltext.]
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2021Binuclear silver(I) complexes with the non-steroidal anti-inflammatory drug tolfenamic acid: Synthesis, characterization, cytotoxic activity and evaluation of cellular mechanism of action
Harurluoglu, Betul; Altay, Ahmet; Caglar, Sema; Kubra Kagan Yeniceri, Esma; Caglar, Bulent; Sibel Şahin, Zarife
In this study, two new binuclear silver(I)-tolfenamic acid complexes including picoline derivative ligands, [Ag2(μ-tolf)2(2-pic)2] 1 and [Ag2(μ-tolf)2(4-pic)2] 2, were synthesized and identified by elemental analysis, FT-IR, 1H NMR and thermal analysis techniques. The in vitro cytotoxicity of the complexes was investigated against human breast cancer cell lines by XTT, flow cytometry, enzyme activity and western blot studies. The structures of 1 and 2 were clarified by single-crystal X-ray diffraction determination. The data clearly indicated that the Ag(I) ion is coordinated to one auxiliary ligand (2-pic or 4-pic), two tolfenamato ligands and another Ag(I) ion, demonstrating a distorted tetrahedral geometry. The tolfenamato ligands act as a bridging bidentate ligands. The chains are stabilized by intramolecular Ag(I)⋯π and π···π interactions. The 1H NMR and thermal analyses displayed the presence of picoline and tolfenamato ligands in the coordination sphere and the purity of the complexes. Both complexes exhibited potent cytotoxicity against cancer cell lines with higher selectivity than carboplatin. Flow cytometry and enzyme activity studies indicated that both complexes caused an increase in apoptosis, ROS and NO levels, cell cycle arrest, mitochondrial membrane damage and caspase activity, as well as inhibiting PI3K/Akt phosphorylation and modulating the oxidant/antioxidant balance system. Western blot analyses revealed the up-regulation of bax, caspase-3, caspase-9 and p53 proteins, but the down-regulation of bcl-2. These results demonstrate the vigorous apoptotic potential of the novel Ag(I) complexes in human breast cancer MDA-MB-453 cells.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2021A novel amperometric H2O2 biosensor constructed by cress peroxidase entrapped on BiFeO3 nanoparticles
Caglar, Bulent; İçer, Fatih; Özdokur, Kemal Volkan; Caglar, Sema; Özdemir, Agah Oktay; Guner, Eda Keles; Beşer, Burcu Meryem; Altay, Ahmet; Çırak, Çağrı; Doğan, Bilge
Herein, we synthesized ferromagnetic BiFeO3 nanoparticles with sizes of 20–60 nm and rhombohedral distorted perovskite structure without any co-formed impurity phases by sol-gel method. Structural, morphological, magnetic, electronic and textural properties of BiFeO3 nanoparticles were characterized by using XRD, SEM-EDX, TEM, FTIR, XPS, VSM, UV-DRS, PL and BET techniques. The peroxidase was isolated from the Cress (Lepidium sativum) and purified by using precipitation of ammonium sulfate and chromatographic techniques; gel filtration and ion exchange chromatography which is showed wide range of thermal stability, maximum activity in the acidic environment and close to the body temperature. Afterwards, a novel amperometric biosensor based on Cress peroxidase entrapped on BiFeO3 nanoparticles modified carbon paste electrode was prepared for the first time to sensitive detection of H2O2. The prepared H2O2 biosensor was operated with the aid of choro-amperometry technique by applying −0.8 V vs Ag/AgCl electrode. The developed biosensor exhibited a linear response towards to H2O2 in the concentration range of 2.0 10−7 to 1.0 10−5 M under the optimal conditions and limit of detection and quantification were estimated as 7.0 10−8 M (2.7 μg L−1) and 2.0 10−7 M (8.7 μg L−1), respectively. The repeatability of the electrode was calculated as 19.2 for 2.0 10−7 M (N = 7) and the accuracy was 81.2% for this concentration. In addition, the H2O2 biosensor exhibited excellent stability up to ten days. Finally, the sensor developed was used for the analysis of H2O2 in milk samples and satisfactory recoveries were obtained under the operating conditions.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2021Isolation, characterization and antiproliferative activity of secondary metabolites from tanacetum alyssifolium (Bornm.) grierson
Köksal, Ekrem; Ulutaş, Yakup; Şimşek, Samed; Bayraktar, Taha; Altay, Ahmet; Çatır, Mustafa; Demirtaş, İbrahim; Tüfekçi, Ali Rıza; Kandemir, Ali; Alp, Cemalettin
Secondary metabolites of Tanacetum alyssifolium (Bornm.) Grierson (Asteraceae) were investigated for the first time. Thirteen compounds including axillarin (1), Luteolin-7-O-β-glucoside (8) and rutin (13) as flavonoids, fraxetin (7), isofraxidin (9), isofraxidin-7-O-glucoside (11) and fraxidin (12) as coumarins, tatridin A (2), altissin (3), tamirin (4) and tanachin (5) as sesquiterpene lactones and 2,4-dihydroxy-6-methoxy acetophenone (6) and picein (10) as acetophenone derivatives were isolated from the methanol extract of the species. The structures of all isolated compounds were elucidated by 1D and 2D-NMR techniques and by comparing with the literature data. In addition, in vitro cytotoxic activity of all isolated compounds was evaluated against breast cancer MCF-7 cell line by XTT assay. Sesquiterpene lactones; tatridin A (2), tamirin (4) and tanachin (5) were found to be the most cytotoxic molecules against MCF-7 cell line.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2021TRINUCLEAR SILVER(I) COMPLEX OF NON-STEROIDAL ANTI-INFLAMMATORY DRUG NAPROXEN: SYNTHESIS, CHARACTERIZATION, AND IN VITRO CYTOTOXICITY
Caglar, Sema; Altay, Ahmet; Harurluoğlu, Betül; Caglar, Bulent
Herein, a new silver(I) complex with the non-steroidal anti-inflammatory drug naproxen and nitrogen donor 3-picoline ligands was synthesized, characterized, and subsequently tested for its cytotoxicity against different types of cancer cell lines. Elemental analysis, Fourier transform infrared spectroscopy, thermal, and proton nuclear magnetic resonance techniques showed that the molecular formula of the prepared complex is bis(3-picoline)tris(μ-naproxenato)trisilver(I) and naproxen ligands bind to silver ions in a bridging bidentate mode. 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) results revealed that silver salts and naproxen alone showed quite weak cytotoxic activity against human breast adenocarcinoma (MDA-MB-453), lung adenocarcinoma (A-549), and colorectal adenocarcinoma (HT-29) cell lines (IC50 > 250 µM), whereas the complex displayed dose dependent cytotoxicity against the aforementioned cell lines. The highest cytotoxicity was observed on MDA-MB-453 cells with an IC50 value of 11.73 µM. Moreover, the complex showed higher selectivity against the cancer cell lines compared to fibroblast 3T3-L1 cells. This study provides preliminary scientific data on the complex for further elucidation of its anticancer mechanism of action.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2019Anatolıan sage Salvıa frutıcosa ınhıbıts cytosolıc glutathıone-s-transferase actıvıty and colon cancer cell prolıferatıon
Altay, Ahmet; Kılıc Suloglu, Aysun; Sagdıcoglu Celep, Gulcın; Selmanoglu, Guldenız; Bozoglu, Faruk
Colorectal cancer is one of the leading causes of death worldwide, and healthy diet is critical in preventing it. This study intends to investigate phenolic profile, antioxidant, and anti-proliferative activity as well as Glutathione S-transferase (GST) inhibition activity of water extract of Salvia fruticosa Mill. (SF.) HPLC analysis revealed that the main bioactive ingredients of SF were rosmarinic and caffeic acid. Total phenolic and flavonoid contents were 425.1 mg GAE/g extract and 94.7 mg CE/g extract, respectively. SF exhibited high antioxidant activity through DPPH and ABTS assays. The extract exhibited time and dose-dependent anti-proliferative activity on colorectal adenocarcinoma cell lines (Caco-2 and HT-29). The extract also inhibited GST activity in a mixed-type manner, with an IC 50 value of 6.8 µg/mL. To conclude, the results suggest that SF may be considered as a medicinal plant which can be used in theprevention and treatment of colon cancer, besides chemotherapy drugs.
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