Sürdürülebilir Kalkınma Amaçları
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- ArticleAçık Erişim2026Antioxidant, Antidiabetic, Antiproliferative Activities, and Verbascoside Content of Four Endemic Verbascum Species: V. leiocarpum, V. ozturkii, V. alyssifolium, and V. tuna-ekimii
Şimşek, Samed; Akşit, Hüseyin; Köksal, Ekrem; Altay, Ahmet
This study, for the first time, investigated the antioxidant, antidiabetic, and antiproliferative properties of methanolic extracts from the aerial and root parts of four endemic Verbascum species—Verbascum leiocarpum Murb., Verbascum ozturkii Karavel., Uzunh. & S.Çelik, Verbascum alyssifolium Boiss., and Verbascum tuna-ekimii Karavel., A.Duran & Hamzaoğlu—and quantitatively determined their verbascoside content using HPLC-DAD. Antioxidant capacity was evaluated by DPPH and FRAP assays, and total phenolic content (TPC) and total flavonoid content (TFC) were also determined. Antidiabetic activity was assessed through α-glucosidase inhibition, and antiproliferative effects were determined in A549, MDA-MB-453, and HT-29 human cancer cell lines. Among the tested samples, the root of V. leiocarpum exhibited the highest TPC (50.89 mg GAE/g extract), FRAP value (124.16 mg TE/g extract), DPPH scavenging ability (IC50: 58.82 μg/mL), and verbascoside content (129.06 mg verbascoside/g extract). This extract also exhibited significant antiproliferative effects against A549 and MDA-MB-453 cells, with inhibition rates of 85% and 69%, respectively. In contrast, both aerial and root extracts of V. tuna-ekimii exhibited low biological activity and a lower concentration of verbascoside. Pearson correlation analysis demonstrated strong positive associations between verbascoside content and both antioxidant and antiproliferative parameters. However, no significant correlation was found between verbascoside content and α-glucosidase inhibition, suggesting that other phytochemicals may be responsible for the antidiabetic activity. These findings indicate that V. leiocarpum, especially its root extract, may be considered a valuable source of natural antioxidants and antiproliferative agents. The study highlights the pharmacological potential of endemic Verbascum species that have not been comprehensively investigated phytochemically or pharmacologically and supports their further evaluation in the context of phytopharmaceutical research.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2026Novel hydrazone-derived pyrazole-benzofuran compounds inhibit cancer cell growth by targeting MMPs, caspases, and PI3K/AKT/mTOR signaling pathway
El Hassani, Issam Ameziane; Altay, Ahmet; Yeniçeri, Esma; Boukharsa, Youness; Assila, Hamza; Alzahrani, Abdullah Yahya Abdullah; Moussa, Sana Ben; Ansar, M'’hammed; Karrouchi, Khalid
In this research, a series of novel pyrazole-benzofuran hydrazone hybrids (3a-h) were designed, synthesis and evaluated for their anticancer potential. All hybrid pyrazole-benzofuran derivatives were purified and characterized by using 1H NMR, 13C NMR, and ESI-HRMS analyses. Their cytotoxic potentials were evaluated against human lung carcinoma (A-549) and colorectal adenocarcinoma (HT-29) cell lines, and mouse fibroblast (3T3-L1) cells using XTT assay. The findings demonstrated that all compounds exhibited a dose-dependent anti-proliferative effect against the cancer cell lines under investigation. Compound 3d was particularly distinguished by its noteworthy IC50 value of 0.28 μM and a selectivity index of 103.85 on A549 cells. Advanced mechanistic anticancer investigations employing flow cytometry revealed that compound 3d triggered apoptosis in A549 cells by inducing mitochondrial membrane disruption and activating multiple caspases. Furthermore, both flow cytometry and Western blot analysis showed that the 3d molecule significantly suppressed the PI3K/AKT/mTOR signaling pathway, which is vital for cellular proliferation. In summary, the findings suggest that compound 3d has the potential to be evaluated as a therapeutic agent for the treatment of lung cancer.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2026Pro-oxidant effect of lobaric acid as a therapeutic strategy against breast cancer: a molecular perspective
Toraman, Emine; Kalın, Şeyda Nur; Bayındırlı, Kübra Nur; Günaydın, Şükran; Keleş, Fatmanur; Altay, Ahmet; Budak, Harun
Background: This study aimed to investigate the anticancer effects of lobaric acid (LA), a lichen acid, in MCF-7 cells. Our previous study demonstrated that LA exhibits anticancer effects by triggering apoptosis in MCF-7 cells. However, the relationship between this anticancer effect and the oxidative pathway and apoptosis mechanism has not been explained. In this study, the cytotoxic and anticancer effects of LA on MCF-7 cells were investigated through oxidative stress and thioredoxin system pathways. Methods and results: For this purpose, reactive oxygen species (ROS), reduced glutathione (GSH), and malondialdehyde (MDA) levels were measured in MCF-7 cells exposed to LA at a concentration of 44.21 µg/mL (IC50). Additionally, the activities, gene, and protein levels of SOD, CAT, GPx, GST, GR, and TrxR enzymes were evaluated. In addition, the expression levels of TXN and TXNIP genes were also analyzed. The results showed that LA increased ROS and MDA levels and decreased GSH levels. Antioxidant enzyme activities (SOD, CAT, GR, TrxR) and protein levels decreased compared to the control, while heterogeneous changes were observed in gene expression levels. Despite increased GPX gene expression, a decrease in enzyme activity and protein levels was observed. While no change in TXN gene expression was observed, protein levels were decreased. TXNIP protein levels were also decreased. Conclusions: The findings provide important data for evaluating lichen-derived compounds as potential anticancer agents targeting redox balance.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2025Chalcone-based imidazo[2,1-b]thiazole derivatives: synthesis, crystal structure, potent anticancer activity, and computational studies
Dadou, Said; Altay, Ahmet; Baydere, Cemile; Anouar, El Hassane; Türkmenoğlu, Burçin; Koudad, Mohammed; Dege, Necmi; Oussaid, Abdelouahad; Benchat, Noureddine; Karrouchi, Khalid
In this work, two novel chalcone-based imidazothiazole derivatives ITC-1 and ITC-2 were synthesized and characterized by 1H NMR, 13C NMR and high-resolution mass spectrometry with electrospray ionization, and chemical structure of ITC-1 was confirmed by single-crystal X-ray diffraction. Also, the anticancer activity of ITC-1 and ITC-2 was evaluated. First, antiproliferative activity tests were performed against cancer cells namely, human-derived breast adenocarcinoma (MCF-7), lung carcinoma (A-549), and colorectal adenocarcinoma (HT-29) cell lines, and mouse fibroblast healthy cell line (3T3-L1) by XTT assay. Afterward, mitochondrial membrane disruption (MMP), caspase activity, and apoptosis tests were performed on MCF-7 cells to elucidate the anticancer mechanism of action of the test compounds by flow cytometry analysis. XTT results revealed that both compounds exhibited a very high degree of antiproliferative effects on each tested cancer cell line with very low IC50 values while showing much lower antiproliferation on 3T3-L1 normal cells with much higher IC50 values. Besides, ITC-2 was determined to have a striking cytotoxic power competing with the chemotherapeutic drug carboplatin. Flow cytometry results demonstrated the mitochondrial-mediated apoptotic effects of both compounds through membrane disruption and multi-caspase activation in MCF-7 cells. Finally, molecular docking studies were performed to determine the structural understanding of the test compounds by their interactions on caspase-3 and DNA dodecamer enzymes, respectively. The interactions between the compound and the crystal structure were determined according to parameters such as free binding energies (ΔGBind), Glide score values, and determination of the active binding site. The obtained data suggest that ITC-1 and ITC-2 may be considered remarkable anticancer drug candidates. In addition to molecular docking via in silico approaches, the pharmacokinetic properties of compounds ITC-1 and ITC-2 were calculated using the Schrödinger 2021-2 Qikprop wizard. Communicated by Ramaswamy H. Sarma.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye20255-methyl-N'-(thiophen-2-ylmethylene)-1H-pyrazole-3-carbohydrazide as potent anticancer agent: Synthesis, spectroscopic characterization, anticancer activity and DFT studies
Hassani, Issam Ameziane El; Brandán, Silvia A.; Altay, Ahmet; Yeniçeri, Esma; Alsalme, Ali; Oulmidi, Afaf; Ansar, M'hammed; Karrouchi, Khalid
A new pyrazole-hydrazide hydrazone derivative, named 5-methyl-N'-(thiophen-2-ylmethylene)-1H-pyrazole-3-carbohydrazide (TMPC) has been synthesized and characterized by FT-IR, UV–Vis, 1H NMR, 13C NMR, and HRMS-ESI. Its cytotoxic activity was tested on various cancer and healthy cell lines using the XTT method. In addition, the advanced anticancer mechanism was investigated by flow cytometry analysis. Hybrid B3LYP/6–311++G** calculations reveal two stable C1 and C2 conformers of TMPC with energy differences of 28.96 kJ/mol in the gas phase and 8.50 kJ/mol in ethanol solution. Comparisons among the experimental NMR, UV and infrared spectra with the predicted ones support the presence of both forms in solution. The presence of dimer C2 justify the intensities and numerous bands observed in the IR spectrum in the 2000–10 cm−1 region. Probably, the repulsion between the N7 and O1 atoms in C1 explain its lower stability and the higher solvation energy (-108.20 kJ/mol) observed for this form in ethanol than C2 (-88.01 kJ/mol). NBO calculations suggest that both forms are stable in the two media while the AIM analyses evidence the higher stability of C2 than C1 due to the N9-H22···N7 interaction observed only for this conformer in the gas phase. Gap values suggest high reactivities of both forms, as compared with similar pyrazole-carbohydrazide species. Full vibrational assignments are reported for both forms of TMPC together with the main scaled force constants. The XTT results showed that TMPC exhibited a selective cytotoxic effect on the tested cancer cell lines in a dose- and time-dependent manner, and also displayed the most potent cytotoxic activity against breast cancer MCF-7 cells with an IC50 value of 22.79 µM after 48 h Flow cytometric analyses showed that TMPC induced apoptosis and suppressed PI3K/Akt signaling in MCF-7 cells.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2025Inhibition of thioredoxin reductase 1 by evernic and vulpinic acids: a promising anticancer strategy on A549 cells
Günaydın, Şükran; Kalın, Şeyda Nur; Sulukoğlu, Emine Karaca; Altay, Ahmet; Budak, Harun
TrxR1 (Thioredoxin reductase 1) is overexpressed in several types of cancer, containing lung cancer, which is closely linked to metastasis. Hence, TrxR1 has emerged as a target for cancer therapies. In this study, it was aimed to survey whether lecanoric (LA), evernic acid (EA), and vulpinic acid (VA) exert an anticancer effect on lung cancer (A549) cells by targeting the TrxR1 protein. The findings indicated that VA elicited a more notable cytotoxic activity in A549 cells (36.21 µg/mL) at a lower IC50 value than EA (139.09 µg/mL). Whereas, LA exhibited very low cytotoxic effect in A549 cells. The flow cytometry and qPCR analyses revealed that VA was superior to EA in inducing apoptosis and necrosis in A549 cells. Moreover, the wound healing assay revealed that both EA and VA considerably inhibited the migration of A549 cells. Furthermore, EA and VA markedly decreased protein expression and enzyme activity of TrxR1 in A549 cells. All these findings revealed that EA and VA possess anticancer activities by targeting TrxR1 in A549 cells. Hence, EA and VA can be proposed as candidates for use as a potential chemotherapeutic agent for lung cancer.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2025Screening of Chemical Profile by LC–MS/MS and Assessment of Biological Properties of Achillea sintenisii Hub. Mor. From Turkey
Köksal, Ekrem; Altay, Ahmet; Altın, Sevgi; Alp, Cemalettin; Ulutaş, Yakup; Şimşek, Samed; Karakuş, Sinem; Akyüz, Sümeyye; Aygül, İmdat; Akşit, Hüseyin
The aim of this study was to determine the secondary metabolites of the n-hexane, ethyl acetate, methanol, and water extracts of Achillea sintenisii Hub. Mor. and to ascertain their divergent biological properties. LC–MS/MS analysis was performed to identify the bioactive compounds. The anticancer properties of the samples were tested against human breast (MCF-7 and MDA-MB-453) and colon (HT-29) cancer cell lines by XTT assay. The anti-Alzheimer's studies were performed using Ellman's assay. The antimicrobial studies were carried out by Kirby–Bauer disc diffusion method. The antioxidative potential of the samples was evaluated on the basis of 2,2-diphenyl-1-picrylhydrazyl scavenging and ferric reducing antioxidant power assays, LC–MS/MS analysis revealed 27 phytochemicals, including high concentrations of quinic acid, gentisic acid, chlorogenic acid, luteolin, cynaroside, and caffeic acid. Ethyl acetate extract exhibited the most potent cytoxicity against MDA-MB-453 cells, with an IC50 value of 83.05 µg/mL. All extracts showed stronger inhibitory activity against acetylcholinesterase and butyrylcholinesterase compared to tacrine. The n-hexane, ethyl acetate, and methanol extracts exhibited considerable antimicrobial activity against Enterococcus faecalis, approaching the level of vancomycin. Methanol extract possessed the highest DPPH scavenging and ferric reducing antioxidant power. These findings render A, sintenisii a promising source for the pharmaceutical, cosmetic, and food industries.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2025Antioxidant and Antiproliferative Activities of Three Endemic Scrophularia Species: S. erzincanica, S. subaequiloba, and S. libanotica var. armena
Ulutaş, Yakup; Köksal, Ekrem; Akşit, Hüseyin; Altay, Ahmet
In this study, methanolic extracts from the aerial parts and roots of three endemic Scrophularia species (Scrophularia erzincanica, Scrophularia subaequiloba, and Scrophularia libanotica var. armena) were evaluated for their antioxidant and antiproliferative activities. Antioxidant potential was determined through total phenolic and flavonoid content, DPPH radical scavenging, and FRAP assays. Antiproliferative effects were assessed against A549 (lung) and MDA-MB-453 (breast) cancer cells using the XTT assay. S. libanotica var. armena had the highest total phenolic content (129.48 mg GAE/g), while S. subaequiloba showed the strongest FRAP activity (200.67 µg TE/g) and DPPH radical scavenging (IC50: 36.83 µg/mL). S. subaequiloba extracts exhibited 83% inhibition against A549 cells and 87% against MDA-MB-453 cells. HPLC–DAD analysis revealed high verbascoside content in S. libanotica var. armena (101.24 mg/g). These findings highlight S. libanotica var. armena as a potent antioxidant source and S. subaequiloba as a promising anticancer agent.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2025Lobaric Acid Exhibits Anticancer Potential by Modulating the Wnt/β-Catenin Signaling Pathway in MCF-7 Cells
Kalın, Şeyda Nur; Bayındırlı, Kübra Nur; Toraman, Emine; Günaydın, Şükran; Keleş, Fatmanur; Altay, Ahmet; Budak, Harun
Lichen secondary metabolites with many remarkable biological activities are used in cancer treatments due to their low side effects and high anticancer potential. In particular, these metabolites constitute an interesting research area in cancer treatments due to their potential to induce apoptosis and suppress metastasis by inhibiting cancer-related signaling pathways. The Wnt/β-catenin signaling pathway plays a role in important biological processes such as oncogenesis, cell cycle regulation, cell proliferation, metastasis, differentiation, apoptosis, and drug resistance. Therefore, inhibition of this pathway is a potential target in cancer therapies. There is no detailed study explaining the potential anticancer molecular mechanism of the lichen secondary metabolite lobaric acid (LA) on breast cancer. Here, it is aimed to investigate the effect of LA on viability, apoptosis, and migration in MCF-7 cells and to elucidate the relationship between the potential anticancer effect and the Wnt/β-catenin signaling pathway. The dose- and time-dependent viability of LA-treated MCF-7 cells was evaluated by XTT assay, and the IC50 value was determined as 44.21 μg/mL at 48 h. LA increased the apoptotic cell population, as shown by flow cytometry analysis, qPCR, and Western blot results. LA inhibited β-catenin by inducing GSK3-β protein expression, thereby suppressing Wnt/β-catenin target genes. LA might be a natural active compound candidate for breast cancer treatment.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2024The Combined Effect of Vulpinic Acid and Doxorubicin in Breast Cancer MCF-7 Cells
Altay, Ahmet; Yeniçeri, Esma Kübra Kağan
Breast cancer is a major global health problem that imposes a significant social and economic burden on individuals and societies. Chemotherapy, a common treatment approach, often leads to resistance and unwanted side effects, especially in the advanced stages of the disease. This has led to a search for more effective and less toxic anticancer agents. Lichens, which are associations of fungi and algae, are gaining attention for their potential in cancer therapy. Lichens are rich sources of secondary metabolites with diverse biological effects, including anti-tumor properties. In this study, we summarise the combined effects of vulpinic acid (VA), a lichen acid, with doxorubicin, a chemotherapeutic drug, on breast cancer MCF-7 cells. The results of the XTT assay and subsequent Compsyn analysis showed that VA and doxorubicin (Dox), a chemotherapeutic drug, alone exhibited potent anti-proliferative effects in a dose- and time-dependent manner, and interestingly, when used in combination, they produced an antagonistic effect in the same cancer line. These results provide the first example of a study to show what effect the combination of VA and Dox will have on other breast cancer cell lines.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2024Phytochemical profile by LC-MS/MS analysis and evaluation of antioxidant, antidiabetic, anti-Alzheimer, and anticancer activity of Onobrychis argyrea leaf extracts
Yeniçeri, Esma; Altay, Ahmet; Koksal, Ekrem; Altın, Sevgi; Taslimi, Parham; Yılmaz, Mustafa Abdullah; Cakir, Oğuz; Tarhan, Abbas; Kandemir, Ali
Introduction: Studies on different species of Onobrychis, a member of the Fabaceae family, have revealed a number of biological activities with potential applications in alternative medicine. The phytochemical content of the plant Onobrychis argyrea subsp. argyrea and some of the important biological activities linked to its metabolism are quite limited. Therefore, this study was the first to determine the content of secondary metabolites in this species and to elucidate important biological activities related to metabolism. Methods: LC-MS/MS was used for the quantitative analysis of bioactive compounds in the aerial part of O. argyrea extracts. The antioxidant properties of the extracts were assessed based on their ability to scavenge DPPH radicals and reduce iron ions. The anti-diabetic effect of the extracts was tested by the inhibition of α-amylase and α-glycosidase enzymes, and the anti-Alzheimer's ability was tested by the inhibition of the enzymes AChE and BChE. The cytotoxic effects of the extracts were tested on four different cancer lines, namely A-549, HT-29, MCF-7 and MDA-MB 453 using the XTT assay. The mechanism of the anti-cancer effect was determined by means of flow cytometry analysis on HT-29 cells. Results: Twenty-nine phytochemicals were identified via the LC-MS/MS analysis in the plant extracts. The most abundant phytochemicals in the extracts were quinic acid, isoquercitrin, epicatechin, and routine, respectively. Antioxidant analysis showed that among all extracts, methanol extract (ME) was most effective in scavenging DPPH (IC50: 23.93 ± 0.96 µg/mL) and in reducing iron ions (53.24 ± 2.14 mgTEAC/g). Enzyme activity studies demonstrated that ME is a potent inhibitor of α-glycosidase (IC50: 15.06±0.64 µg/mL), AChE (IC50: 24.75±0.76 µg/mL), and BChE (IC50: 3.36±0.14 µg/mL). XTT assay results disclosed the strongest anti-proliferative activity of ME against the human colorectal adenocarcinoma HT-29 cell line with an IC50 value of 33.35±0.92 µg/mL. Flow cytometry analysis revealed that ME caused mitochondrial membrane damage in HT-29 cells (**p<0.01) and subsequently induced apoptosis (**p<0.01) by activating the caspase pathway (**p<0.001). Conclusion: O. argyrea, rich in bioactive compounds, showed remarkable antioxidant, antidiabetic, Alzheimer's, and anticancer properties in vitro, demonstrating that this plant contains secondary metabolites that may be potential drug candidates for the treatment of metabolic diseases.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2024The non-steroidal anti-inflammatory drugs based on Zinc(II) picoline complexes: Synthesis, characterization, and evaluation of antiproliferative effects against human breast adenocarcinoma MDA-MB-453 cells by inducing ROS-mediated apoptosis and down-regulating PI3K/AKT signaling pathway
Caglar, Sema; Polat, Tuğba; Altay, Ahmet; Yeniçeri, Esma; Caglar, Bülent
This work aims to synthesize zinc(II) non-steroidal anti-inflammatory complexes and to evaluate their anticancer abilities on different cancer cell lines. In this context, four new zinc(II) complexes including the NSAIDs mefenamic acid or niflumic acid and picoline derivatives {[Zn2(μ-mef)3(3-pic)2] 1, [Zn3(μ-mef)6(2-pic)2] 2, [Zn3(μ-mef)6(4-pic)2] 3 and [Zn(nif)2(4-pic)2]} 4 were synthesized. The molecular structures were identified by elemental analysis, FT-IR, 1H NMR (complexes 2 and 3), UV–Vis, thermal analysis, and X-ray diffraction (complexes 1 and 4), indicating that one complex was mononuclear, one complex was binuclear, and two complexes were trinuclear. The deprotonated mefenamato ligands bind to the zinc(II) ion via carboxylate oxygen atoms and chelate in a bridging bidentate asymmetric form. The deprotonated niflumato ligand acts as a monodentate ligand. UV–Vis spectroscopy was used to assess the complexes' stability. The stoichiometry of the synthesized complexes was determined by 1H NMR and thermal studies. XTT assays showed that all complexes exhibited dose-dependent antiproliferative effects against breast cancer MCF-7 and MDA-MB-453 cells, colon cancer HT-29 cells, and lung cancer A549 cells. The highest cytotoxicity was exhibited by complex 3 against MDA-MB-453 cells with an IC50 value of 8.28 µM. The mechanistic studies performed by flow cytometry revealed that complex 3 exerted its in vitro anticancer activity against MDA-MB-43 cells by inducing apoptosis, increasing ROS production, and inhibiting the PI3K/AKT signaling pathway.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2024Synthesis, Characterization, Investigation of Anticancer Activity and Molecular Docking Studies of N2O2 Type Schiff Base Ligand and Metal Complexes
Türkmenoğlu, Mustafa; Yıldırım, Sümeyra Tuna; Altay, Ahmet; Türkmenoğlu, Burçin
Schiff base ligands and their metal complexes play a great important role in pharmaceutical sciences because of their wide and significant activities. They are versatile pharmacophores for the design and discovery of many drugs. In this study, a Schiff base ligand and its complexes were synthesized. Some spectroscopic techniques such as FT-IR, 1H-NMR, 13C-NMR, XRD, SEM, and UV-Vis were used for structural characterization. Antiproliferative activities of the synthesized ligand and complexes were investigated on the human breast (MCF-7) and colon (HT-29) cancer cell lines by XTT [2,3-Bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium] method. The obtained data showed that the ligand and complexes exhibited dose-dependent and cell-selective in vitro antiproliferative activity on the tested cell line. In addition, it was determined that complexes showed statistically higher cytotoxic activity compared to the ligand. The binding parameter values and the important amino acids in the binding site were determined between the possible lead compounds synthesized by molecular docking from in silico approaches and the target. A molecular docking study of the cobalt complex was performed against Bcl-2 (PDB ID:4IEH) and DNA recognition (PDB ID:423D) targets. In conclusion, these data show that the synthesized Schiff base ligand and metal complexes have the potential to be evaluated as a chemotherapeutic agent.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2024Novel isoniazid-hydrazone derivatives induce cell growth inhibition, cell cycle arrest and apoptosis via mitochondria-dependent caspase activation and PI3K/AKT inhibition
Rouzi, Khouloud; Altay, Ahmet; Bouatia, Mustapha; Yeniçeri, Esma; Islam, Mohammad Shahidul; Oulmidi, Afaf; El Karbane, Miloud; Karrouchi, Khalid
In this study, seven isoniazid-hydrazone derivatives (3a-g) were synthesized and their structures elucidated by chromatographic techniques, and then the antiproliferative effects of these compounds on various cancer cells were tested. The advanced anticancer mechanism of the most potent compound was then investigated. Antiproliferative activities of the synthesized compounds were evaluated on human breast cancer MCF-7, lung cancer A-549, colon cancer HT-29, and non-cancerous mouse fibroblast 3T3-L1 cell lines by XTT assay. Flow cytometry analysis were carried out to determine cell cycle distribution, apoptosis, mitochondrial membrane potential, multi-caspase activity, and expression of PI3K/AKT signaling pathway. The XTT results showed that all the title molecules displayed cytotoxic activity at varying strengths in different dose ranges, and among them, the strongest cytotoxic effect and high selectivity were exerted by 3d against MCF-7 cells with the IC50 value of 11.35 µM and selectivity index of 8.65. Flow cytometry results revealed that compound 3d induced apoptosis through mitochondrial membrane disruption and multi-caspase activation in MCF-7 cells. It also inhibited the cell proliferation via inhibition of expression of PI3K/AKT and arrested the cell cycle at G0/G1 phase. In conclusion, all these data disclosed that among the synthesized compounds, 3d is notable for in vivo anticancer studies.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2024Diffractaic acid exerts anti-cancer effects on hepatocellular carcinoma HepG2 cells by inducing apoptosis and suppressing migration through targeting thioredoxin reductase 1
Sulukoğlu, Emine Karaca; Günaydın, Şükran; Kalın, Şeyda Nur; Altay, Ahmet; Budak, Harun
Hepatocellular carcinoma (HCC) represents one of the most common malignant tumors worldwide. Due to the limited number of available drugs and their side effects, the development of new chemotherapeutic strategies for HCC treatment has become increasingly important. This study is aimed at investigating whether diffractaic acid (DA), one of the secondary metabolites of lichen, exhibits a potential anticancer effect on HepG2 cells and whether its anticancer effect is mediated by inhibition of thioredoxin reductase 1 (TRXR1), which is a target of chemotherapeutic strategies due to overexpression in tumor cells including HCC. XTT assay results showed that DA exhibited strong cytotoxicity on HepG2 cells with an IC50 value of 78.07 µg/mL at 48 h. Flow cytometric analysis results revealed that DA displayed late apoptotic and necrotic effects on HepG2 cells. Consistent with these findings, real-time PCR results showed that DA did not alter the BAX/BCL2 ratio in HepG2 cells but upregulated the P53 gene. Moreover, the wound healing assay results revealed a strong anti-migratory effect of DA in HepG2 cells. Real-time PCR and Western blot analyses demonstrated that DA increased TRXR1 gene and protein expression levels, whereas enzyme activity studies disclosed that DA inhibited TRXR1. These findings suggest that DA has an anticancer effect on HepG2 cells by targeting the enzymatic inhibition of TRXR1. In conclusion, DA as a TRXR1 inhibitor can be considered an effective chemotherapeutic agent which may be a useful lead compound for the treatment of HCC.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2023Effect of evernic acid on human breast cancer MCF-7 and MDA-MB-453 cell lines via thioredoxin reductase 1: A molecular approach
Kalın, Şeyda Nur; Altay, Ahmet; Budak, Harun
Thioredoxin reductase 1 (TrxR1) has emerged as an important target for anticancer drug development due to its overexpression in many human tumors including breast cancer. Due to the serious side effects of currently used commercial anticancer drugs, new natural compounds with very few side effects and high efficacy are of great importance in cancer treatment. Lichen secondary metabolites, known as natural compounds, have diverse biological properties, including antioxidant and anticancer activities. Herein, we aimed to determine the potential antiproliferative, antimigratory, and apoptotic effects of evernic acid, a lichen secondary metabolite, on breast cancer MCF-7 and MDA-MB-453 cell lines and afterward to investigate whether its anticancer effect is exerted by TrxR1-targeting. The cytotoxicity results indicated that evernic acid suppressed the proliferation of MCF-7 and MDA-MB-453 cells in a dose-dependent manner and the IC50 values were calculated as 33.79 and 121.40 μg/mL, respectively. Migration assay results revealed the notable antimigratory ability of evernic acid against both cell types. The expression of apoptotic markers Bcl2 associated X, apoptosis regulator, Bcl2 apoptosis regulator, and tumor protein p53 by quantitative real-time polymerase chain reaction and western blot analysis showed that evernic acid did not induce apoptosis in both cell lines, consistent with flow cytometry results. Evernic acid showed its anticancer effect via inhibiting TrxR1 enzyme activity rather than mRNA and protein expression levels in both cell lines. In conclusion, these findings suggest that evernic acid has the potential to be evaluated as a therapeutic agent in breast cancer treatment.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2023Isolation, characterization and anticancer activity of secondary metabolites from Verbascum speciosum
Demirci, Serpil; Alp, Cemalettin; Akşit, Hüseyin; Ulutaş, Yakup; Altay, Ahmet; Yeniçeri, Esma; Köksal, Ekrem; Yaylı, Nurettin
Herein, two iridoid glucosides aucubin (1) and ajugol (2), and two phenyl ethanoids, verbascoside (3) and poliumoside (4) were isolated from the methanol extract of the aerial parts of Verbascum speciosum and used to study about their anticancer activity for the first time. The structures of all compounds were elucidated using spectroscopic data (IR, 1D and 2D NMR, LC-TOF/MS). Antiproliferative activities of Aucubun (1) and Verbascoside (3) were tested against A-549 (human colon cancer), MDA-MD-453 (human breast cancer) and 3T3-L1 (mouse fibroblast)cell lines by XTT assay. In addition, the anticarcer mechanism of action of aucubin (1) was investigated on MDA-MB-453 cells for the first time. XTT result showed that both applied compounds exhibited antiproliferative effect at different dose ranges depending on the cancer type, as well as selectivity between cancer and healty cell lines. Flow cytometry analyzes revealed that aucubin (1) exerts its cytotoxic effect in MDA-MB-453 cells by directing cells to early apoptosis and inhibiting the P13K/AKT signaling pathway.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2023Isolation and cytotoxic activities of undescribed iridoid and xanthone glycosides from Centaurium erythraea Rafn. (Gentianaceae)
Akşit, Hüseyin; Gözcü, Sefa; Altay, Ahmet
Centaurium erythraea Rafn. (Gentianaceae) is used in internal traditional therapy as an anthelmintic, hypotensive, antipyretic, and antidiabetic. It is used externally for the treatment of wounds. Ursolic acid, maslinic acid, secologanin, secologanin dimethyl acetal, centauroside A, erythraeaxanthone I, erythraeaxanthone II, and demethyleustomin were isolated from aerial parts of Centaurium erythraea and were identified using spectroscopic methods, including NMR and mass spectrometry. The cytotoxic potency of undescribed compounds was evaluated by the XTT assay against human breast cancer MCF-7, MDA-MB-453 and mouse fibroblast 3T3-L1 cell lines. Erythraeaxanthone II was found to have the most potent cytotoxic activity.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2023Novel Pyrazole-Based Benzofuran Derivatives as Anticancer Agents: Synthesis, Biological Evaluation, and Molecular Docking Investigations
Ameziane El Hassani, Issam; Altay, Ahmet; Karrouchi, Khalid; Yeniçeri, Esma; Türkmenoğlu, Burçin; Assila, Hamza; Boukharssa, Youness; Ramli, Youssef; Ansar, M'hammed
In this work, the design, synthesis, and mechanistic studies of novel pyrazole-based benzofuran derivatives 1–8 as anticancer agents were discussed. Cytotoxic potency of the title compounds was evaluated against the lung carcinoma A-549, human-derived colorectal adenocarcinoma HT-29, breast adenocarcinoma MCF-7 cells as well as mouse fibroblast 3T3-L1 cells using XTT assay. Anticancer mechanistic studies were carried out with flow cytometry. XTT results revealed that all compounds exhibited dose-dependent anti-proliferative activity against the tested cancer cells, and especially compound 2 showed the strongest anti-proliferative activity with an IC50 value of 7.31 μM and the highest selectivity (15.74) on MCF-7 cells. Flow cytometry results confirmed that the cytotoxic power of compound 2 on MCF-7 cells is closely related to mitochondrial membrane damage, caspase activation, and apoptosis orientation. Finally, molecular docking studies were applied to determine the interactions between compound 2 and caspase-3 via in-silico approaches. By molecular docking studies, free binding energy (ΔGBind), docking score, Glide score values as well as amino acid residues in the active binding site were determined. Consequently, these results constitute preliminary data for in vivo anticancer studies and have the potential as a chemotherapeutic agent.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2023Diffractaic acid exhibits thioredoxin reductase 1 inhibition in lung cancer A549 cells
Günaydın, Şükran; Sulukoğlu, Emine Karaca; Kalın, Şeyda Nur; Altay, Ahmet; Budak, Harun
Lung cancer is the leading cause of cancer-related deaths all over the world. Therefore, it has gained importance in the development of new chemotherapeutic strategies to identify anticancer agents with low side effects, reliable, high anticancer potential, and specific to lung cancer cells. Thioredoxin reductase 1 (TrxR1) is an important therapeutic target for lung cancer treatment because of its overexpression in tumor cells. Here, we aimed to examine the anticancer effect of diffractaic acid, a lichen secondary metabolite, in A549 cells by comparing it with the commercial chemotherapeutic drug carboplatin and also to investigate whether the anticancer effect of diffractaic acid occurs via TrxR1-targeting. The IC50 value of diffractaic acid on A549 cells was determined as 46.37 μg/mL at 48 h, and diffractaic acid had stronger cytotoxicity than carboplatin in A549 cells. qPCR results revealed that diffractaic acid promoted the intrinsic apoptotic pathway through the upregulation of the BAX/BCL2 ratio and P53 gene in A549 cells, which is consistent with the flow cytometry results. Furthermore, migration analysis results indicated that diffractaic acid impressively suppressed the migration of A549 cells. While the enzymatic activity of TrxR1 was inhibited by diffractaic acid in A549 cells, no changes were seen in the quantitative expression levels of gene and protein. These findings provide fundamental data on the anticancer effect of diffractaic acid on A549 cells targeting TrxR1 activity, suggesting that it could be considered a chemotherapeutic agent for lung cancer therapy.
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