Browsing by Author "Yilmaz, Can"

Now showing 1 - 20 of 21

The Activities of Gst Isozymes in Stomach Tissues of Female Obese Patients
(Walter de Gruyter Gmbh, 2020) Yilmaz, Can; Bulus, Hakan; Oguztuzun, Serpil; Cihan, Mehmethan; Fidan, Ceylan
Objectives: Obesity has become an important public health problem because of its increasing prevalence and relation with many diseases and mortality. Studies have shown its association with oxidative stress. In this study, the effect of obesity on total amount of thiol and some glutathione S-transferase (GST) isozymes were investigated which could serve as an important criteria in dose adjustment of some certain drugs in obese. Methods: The gastric tissues removed by gastrectomy operation from 29 morbid obese female patients were analysed for thiol levels and activities of total GST, GSTT1-1 and GSTM1-1. Patients were grouped according to age, presence of hypertension and/or diabetes, and family history. Results: The average total thiol was 131.22 (+/- 7.74) nmol/mg protein with no significant differences in between the groups. GSTT1 specific activities were about 20% higher in four groups: with ages over 35 years old, with hypertension, without diabetes and finally without family history, with respect to other groups. The differences between total GST and GSTM1 activity levels of experimental groups were not significant. Conclusions: This is the first study to compare activities of GST isozymes and total thiol content in the stomach tissues of obese female patients accompanying some common metabolic disorders, age and family history.
Bisphenol S Leads To Cytotoxicity-Induced Antioxidant Responses and Oxidative Stress in Isolated Rainbow Trout (Oncorhyncus Mykiss) Hepatocytes
(Springer, 2021) Kaptaner, Burak; Yilmaz, Can; Aykut, Handan; Dogan, Emine; Fidan, Ceylan; Bostanci, Muserref; Yildiz, Fatos
Background Bisphenol S (BPS) is a chemical compound that is utilized in the plastic industry as an alternative to bisphenol A (BPA). The toxic effects of BPS in fish is less known and limited. Therefore, in the present study, the influence of BPS on rainbow trout (Oncorhyncus mykiss) hepatocytes in vitro was investigated. Methods and results For this purpose the fish hepatocytes were isolated, and then the cultured cells were treated with increasing concentrations of BPS (0, 15.63, 31.25, 62.50, 125, 250, and 500 mu M) for 24 h. The cytotoxic impact of BPS was determined in the culture media using lactate dehydrogenase assay and then, the antioxidant defence indicators were assayed. The results showed that concentration-dependent increases were observed in the percentage of cytotoxicity. The superoxide dismutase activity was reduced, while the catalase and glutathione peroxidase activity increased with all of the BPS concentrations. The glutathione S-transferase (GST) activity significantly increased after a BPS concentration of 31.25 mu M or higher, while GST Theta 1-1 activity was decreased by the same concentrations of BPS. The reduced glutathione content significantly decreased with a BPS concentration of 31.25 mu M or higher, and the malondialdehyde content increased after BPS concentrations of 125, 250, and 500 mu M. Conclusions The findings determined herein suggested that BPS causes cytotoxicity in fish hepatocytes and can lead to oxidative stress, resulting hepatotoxic in fish. Thus, the utilization of BPS instead of BPA as safe alternative in industry should be re-evaluated in the future for environmental health.
A Combined Method of Protein Extraction From Unorthodox Plant Samples for Proteomics
(Bentham Science Publ Ltd, 2021) Yilmaz, Can; Iscan, Mesude
Aim: This study aimed to generate an improved method of protein extraction and purifi-cation from plant tissues containing very high amounts of phenolic compounds and other interfer-ing biomolecules. Background: Protein extraction at proteomic studies on some plant species, including conifers, is challenging, and the yield and quality are unpredictable. Objective: Two popular protocols were combined with each other to construct a novel one with en-hanced abilities to produce higher purity of samples compatible for high precision molecular sys-tems and analysis. Methods: The new method was compared with the other two for their efficiencies in classical SD-S-PAGE, 2-DE and capillary chromatography applications. Results: All three methods were comparable in SDS-PAGE procedure; however, only the new method created acceptable gel images in 2-DE. Bioanalyzer results, also, demonstrated that the new method provided protein samples pure enough to be used in capillary chromatography with 2 times more peaks in electropherograms with lower noise and higher total relative protein concentra-tions closest to the applied amount. Conclusion: The new combined method is a successful alternative for plant proteomicists with higher yield and quality of proteins from recalcitrant tissues. Other: The new method could be preferred, especially, for high-tech, sensitive proteomic analysis.
Comparison of Short-Term Physiological and Biochemical Effects of Drought Stress on Two Wheat Cultivars
(inst Tecnologia Parana, 2023) Yilmaz, Pinar; Babat, Ceylan Fidan; Yilmaz, Can
Drought stress, which is becoming more frequent and severe, restricts grain production. It is critical to choose wheat (Triticum aestivum L.) cultivars that are drought-resistant enough in progressively arid climates. Early physiological and biochemical responses were measured by applying drought stress to susceptible Bezostaja-1 and tolerant Tosunbey wheat cultivars with three different PEG-6000 concentrations to understand the reliability, selectivity and practicality of tested parameters. Depending on the elevated drought, lengths, fresh-dry-turgor weights, relative water content of both root and stem decreased, and chloropyll amounts increased similarly but in different dimensions in both cultivars. While a decrease was observed in the total thiol content of both, it was determined that this value was 10 times higher in Bezostaja-1 cultivar. While proline amounts peaked at the most severe drought, this value was found to be 2.5 times higher in Bezostaja-1 than in Tosunbey. The protein content is 35% higher in Bezostaja-1. In contrast to glutathione S-transferase theta1 (GSTT1) isozyme, total GST activity increased 53.1% in Bezostaja-1 and 33.6% in Tosunbey, compared to control. This average values are about three times higher in Bezostaja-1 compared to Tosunbey. Of the experimental groups whose band profiles were generated by SDS-PAGE and compared with UPGMA and neighbor-joining methods, moderate to high drought samples of Bezostaja-1 showed explicitly different results and possibly a metabolically distinct response from all others. Besides frequently used ones, total thiol content, total GST activity and changes in the protein bands could be used as useful parameters in the selection of drought-resistant cultivars.
Describing the Expression Profiles of Glutathione S-Transferase Mu and Tumor Protein 53 in Brain Tumor Tissue
(Erciyes Univ Sch Medicine, 2024) Dirican, Onur; Kaygin, Pinar; Lti, Sezen Yilmaz Saria; Yilmaz, Can; Simsek, Gulcin; Oguztuzun, Serpil; Izci, Yusuf
Objective: This study aims to explore the expression profiles of the glutathione S-transferaseMu (GST-M) isozyme and tumor protein 53 (p53) in both healthy and tumorous brain tissues. The findings are compared with clinical features and lifestyle factors to identify potential associations or correlations. Materials and Methods: We retrospectively analyzed the medical records of 149 patients diagnosed with primary or metastatic intracranial tumors. The expression levels of GST-M and p53 proteins were assessed in healthy and tumorous brain tissues using immunohistochemical staining. We also evaluated the associated clinical features and lifestyle factors. Results: There was a significant difference in the expression levels of GST-M between tumorous and healthy brain tissues, with tumor tissues showing higher expression (p<0.0001). Conversely, robust p53 expression was absent in both normal (97.3%) and tumor (78.5%) tissues. Nevertheless, a significantly higher prevalence of samples with p53 expression was found in the tumor group (p<0.0001). No associations were found between expression levels and clinical features or lifestyle risk factors. Furthermore, GST-M and p53 expression did not impact postoperative survival rates. Conclusion: The findings indicate an elevated expression of GST-M in brain tumor tissues, suggesting a potential role for GST-M in brain tumorigenesis.
Design, Synthesis, and in Vitro Evaluation of Thieno[A]dibenzothiophene Derivatives
(Wiley-v C H verlag Gmbh, 2020) Konus, Metin; Algso, Muheb A. S.; Kavak, Emrah; Kurt-Kizildogan, Aslihan; Yilmaz, Can; Kivrak, Arif
A variety of highly substituted thieno[2,3-a]dibenzothiophenes and thieno[3,2-a]dibenzothiophenes are readily prepared via cascade electrophilic cyclization reaction. The reaction was tolerated a variety of compounds. In the present study, antimicrobial and antifungal activities were investigated for all synthesized molecules against A. niger ATCC 16404, C. albicans ATCC 10231, S. aureus ATCC 25923 and B. subtilis ATCC 6633, respectively.
Determination of Antioxidant, Antimicrobial and Anticancer Properties of Newly Synthesized 2-Methoxyphenyl Thiophene Derivatives
(Wiley-v C H verlag Gmbh, 2024) Cetin, Dogan; Konus, Metin; Yilmaz, Can; Arslan, Sevki; Abdelsalam, Aminehafis; Hutanu, Elena Daniela; Kivrak, Arif
In this study, antioxidants, anticancer, and antimicrobial properties of four newly synthesized thiophene derivatives were investigated. In addition, basic ADME properties were calculated in silico. According to the study's findings, tested compounds antioxidant activity was weaker than the standards in both the FRAP and ABTS assays. The MTT analysis revealed that the chemicals 3 and 4 were cytotoxic to every cancer cell line that was tested. 3 and 4 increased the rate of apoptosis in the tested cancer cells at levels close to that in the positive control group. The gene expression levels of apoptotic markers (BAX, Bcl-2, Casp-3, -8, and -9) detected at all cell lines after incubation with 3 and 4 were changed as expected for apoptotic agents, except Bcl-2 of HT-29. It was concluded that the addition of bromine to C2 of thiophene cycle of 3, resulted 4 with greater apoptotic potential probably because of a change in molecular conformation and ligand exchange kinetics. Compound 3 was found to have antifungal activity against Aspergillus niger, while 4 was found to have antibacterial activity on gram-positive bacteria. In silico ADME/T analysis revealed that 3 and 4 were able to pass through the gastrointestinal tract lumen and blood-brain barrier.
The Effects of Water Quality and Brewing Type on Total Antioxidant Capacity in Herbal Teas
(Kahramanmaras Sutcu Imam Univ Rektorlugu, 2021) Yilmaz, Can; Konus, Metin; Fidan, Ceylan; Ergin, Derya; Cetin, Dogan; Dilek, Zeynep; Elasan, Esma
The antioxidant capacity of the polyphenols is the basis of the potential health benefits of herbal tea consumption. In this study. the effects of infusion time. presence of tea packs and water quality on the extraction yield of polyphenolic compounds providing antioxidant activity of melissa, rosehip, fennel, camomile and white tea, which are commonly consumed in Turkey. were investigated. Antioxidant activities were determined by using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. The results of the study showed that the antioxidant activity of herbal teas brewed with distilled water was higher than that in tap water, and that antioxidant activity increased for these teas due to the increased infusion time. When tap water was used, it was determined that a higher antioxidant activity was obtained as a result of brewing for 3 minutes for rosehip and melissa tea and 10 minutes for white tea. The results also showed that packaged brewing for rosehip and fennel tea; and, unpackaged brewing for chamomile, melissa, and white tea resulted in higher antioxidant activity.
Glutathione S-Transferase Enzyme Activity and Protein Expression in Patients With Recurrent Tonsillitis and Idiopathic Tonsillar Hypertrophy
(Palacky Univ, Medical Fac, 2019) Aydin, Sedat; Demir, Mehmet Gokhan; Oguztuzun, Serpil; Kilic, Murat; Yilmaz, Can; Dirican, Onur
Objectives. The palatine tonsil is a significant part of the secondary immune system. Tonsillitis and idiopathic tonsillar hypertrophy (ITH) are the most common pathologies of this component. Although there are studies on their pathogenesis, there is insufficient study of the role of antioxidant agents. Glutathione S-transferase (GST) isozymes contribute to the antioxidation reactions in the tissue via the glutathione pathway. The purpose in this study was to reveal the levels of the GST enzyme activity and protein expression of GSTP1 and GSTA1 isozymes in patients with tonsillitis and tonsil hypertrophy, and to investigate their role in the pathogenesis of these diseases. Materials and Methods. Sixteen patients with recurrent tonsillitis and 5 patients with ITH and were included in the study. Cytosolic extracts were prepared from post-tonsillectomy tissues of both patient groups and GST enzyme activities were measured. Results. The expression of GSTP1 was found to be significantly higher than GSTA1 in tissue samples of patients with ITH and recurrent tonsillitis (P<0.001). Increased GST activity and GSTP1 isozyme expression were shown in patients with recurrent tonsillitis compared to the idiopathic tonsillar hypertrophy study group.There was a positive correlation between the expressions of GSTP1 (P=0.040; r=0.47). Conclusion. Increased GST activity and GSTP1 isozymes were demonstrated histologically in the pathogenesis of ITH and recurrent tonsillitis. We believe that the data of changes in antioxidant capacity, obtained from studies with more extensive and larger samples, would support our findings.
Identification of 3-Bromo as a Potent Anticancer Agent With Promising Inhibitory Effects on Gst Isozymes
(Bentham Science Publ Ltd, 2021) Yilmaz, Can; Arslan, Sevki; Mutlu, Dogukan; Konus, Metin; Kayhan, Abdussamet; Kurt-Kizildogan, Aslihan; Kivrak, Arif
Background: Indole-based heterocyclic compounds play important roles in pharmaceutical chemistry due to their unexpected biological and pharmacological properties. Objective: Herein, we describe novel biological properties (antioxidant, antimicrobial and anti-cancer) of 3-bromo-1-ethyl-1H-indole (BEI) structure. Method: BEI was synthesized from 1-Methyl-2-phenylindole and N-bromosuccinimide and was characterized by using 1H and 13C NMR. Cytotoxicity was determined by MTT assay. Apoptosis analysis of BEI was determined by Arthur (TM) image-based Cytometer. Different methods were applied to assess the antioxidant activity of BEI. Molecular docking studies were conducted to determine the interactions of bonding between GST isozymes and BEI. Results: According to the antioxidant and antimicrobial activity assays, BEI compound showed reduced total antioxidant activity compared to the Trolox standard, whereas it showed moderate antimicrobial activity against Aspergillus niger and Phytophora eryhtrospora. Notably, the BEI compound demonstrated substantial selective cytotoxicity for the first time towards cancer cell lines, and there existed a significant decrease in the percentage of live cells treated with BEI, in comparison to the control ones. Interestingly, BEI exhibited a promising glutathione S-transferase isozymes inhibition. Conclusion: The results of this study suggest that BEI seems to be a promising molecule to be used in the design of new anti-cancer agents that provide superiority to present commercial anti-cancer drugs.
Impact of Beneficial Microorganisms Inoculated Cotton Plants on Spodoptera Exigua (Lepidoptera: Noctuidae)
(Entomological Soc Brasil, 2024) Kizilkan, Nurhan Didem; Konus, Metin; Risvanli, Mehmet Ramazan; Yilmaz, Can; Kara, Hilmi; Ozgokce, Mehmet Salih; Atlihan, Remzi
This study discusses plant-mediated effects of beneficial soil-borne microorganisms on population growth parameters of Spodoptera exigua (Lepidoptera: Noctuidae), a major cotton pest. In particular, we investigated the impact of these microorganisms on oxidative stress, chlorophyll content, and sugar and protein levels in cotton plants, and how these changes in the plant affect the survival, development, reproduction, and ultimately population growth of the pest. A longer preadult period, lower preadult survival rate, and lower reproduction were obtained for the pest cohort feeding on treated plants, which resulted in lower population parameters, i.e., intrinsic growth rate, finite growth rate, and net reproduction rate. The population projection results showed the same trend as the population parameters. These results can be attributed to the changes caused by microorganisms in the treated plants. There was no oxidative stress in the treated plants. Instead, the chlorophyll content in these plants increased, and the protein-carbohydrate ratio decreased. Additionally, we assessed the effects of plant-insect-microorganisms interaction on total glutathione levels, glutathione S-transferase, and esterase enzyme activities in S. exigua. Overall results indicate that beneficial microorganisms tested enhance the plant's ability to defend against the pest. Additionally, the findings from this study provide valuable insights into the complex interplay among plants, microorganisms, and pests, offering potential strategies for incorporating these interactions into pest management practices.
In Vitro and in Silico Evaluation of Inhibitory Effects of Bisphenol Derivatives on Acetylcholinesterase of Electric Eel (Electrophorus Electricus L.)
(Elsevier Science inc, 2022) Yilmaz, Can; Khorsheed, Waleed Mohammed; Babat, Ceylan Fidan
The inhibitory effects of bisphenol A (BPA) and bisphenol S (BPS), which are common pollutants, especially in marine and freshwater, on the electric eel acetylcholinesterase (AChE) activity were studied in vitro and in silico. Both produced full non-competitive inhibition, but the Ki value of BPA was half that of BPS. Molecular docking analyses revealed that both interact with residues W286, F297, Y337, F338 in the PAS and ABS regions in the middle and entrance of the active site gorge, and that BPS also has hydrogen bond with S203 of the catalytic triad. The surge at IC50 values of both compounds with an inflection point at pH: 8.2 suggested that Y124 and/or Y337 in the narrow gorge are primary structural factors in binding. Less effective inhibition of BPS, especially at 25-30 degrees C, the temperature at which enzyme activity peaks, was attributed to the conformation of the narrow gorge. Homology analyses for AChE initially revealed a significant degree of identity, particularly in the alpha/ beta hydrolase domain, which also comprises the active site, with sequences from seven distinct teleost species of various environments. Finally, it was discovered for the first time that BPS, like BPA, is a significant inhibitor of AChE, and this was confirmed by in vitro and in silico analyses done at various pH and temperature levels. It was concluded that this effect might also apply to AChE of most other bony fish.
Synthesis and Biological Activity of New Indole Based Derivatives as Potent Anticancer, Antioxidant and Antimicrobial Agents
(Elsevier, 2022) Konus, Metin; Cetin, Dogan; Kizilkan, Nurhan Didem; Yilmaz, Can; Fidan, Ceylan; Algso, Muheb; Arslan, Sevki
Indoles have very critical roles to design new biologically active molecules in medicinal chemistry. They display higher biological activities or create new biological properties when compared to the other heteroaromatic compounds. In the present study, 1-ethyl-2-phenyl-3-(thiophen-2-yl)-1H-indole (3), 8-ethyl-8H-benzo[a]thieno[3,2-c]carbazole (4), 1-ethyl-2-phenyl-3-(5-(phenylethynyl)thiophen-2-yl)-1H-indole (6) and 1-ethyl-3-(furan-2-yl)-2-phenyl-1H-indole (7) are prepared via Pd-catalyzed cross-coupling reactions and iodocyclization reactions. It was determined that compound 3 and 7 were also seemed to be better drug candidates at the end of in silico evaluation. Furthermore, compound 7 provided the best antibacterial and antifungal activity against the test indicator strains. It showed a potent antifungal effect on Aspergillus niger ATCC 16404 (MIC: 1.17 mu g mL(-1); MFC: 2.7 mu g mL(-1)). In addition, while compounds 3, 6 and 7 showed significantly high molybdenum reducing activity compared to trolox, 7 exhibited almost the same antioxidant activity (EC50 = 7.1 mu M) compared to the trolox standard (EC50 = 5.07 mu M). After characterization, the cytotoxic activities of novel indoles were tested against different cancer cell lines and non-cancerous human cell line. Compound 3 and 7 had selective cytotoxic activity towards cancer cells. EC50 values of compound 3 were found to be 248.15 mu M for LnCap, 139.81 mu M for HepG2, and 164.72 mu M for the Caco-2 cell line. Similarly, The EC50 value of 7 was found as 38.725 mu M for LnCap, 70.02 mu M for HepG2, and 86.98 mu M for Caco-2, and 90.97 mu M for Hek293 cell line. Moreover, it was revealed that these two compounds showed strong apoptotic properties towards these cancer cell lines as described by image cytometry and real time PCR. Consequently, these results improved that our molecules 3 and 7 could be new candidates as anticancer agents and apoptosis inducers. (C) 2022 Elsevier B.V. All rights reserved.
Synthesis and Biological Evaluation of Novel Benzothiophene Derivatives
(indian Acad Sciences, 2018) Algso, Muheb A. S.; Kivrak, Arif; Konus, Metin; Yilmaz, Can; Kurt-Kizildogan, Aslihan
Benzothiophene derivatives were synthesized regioselectively using coupling reactions and electrophilic cyclization reactions. Antimicrobial properties of isolated compounds were tested against indicator microorganisms such as C. albicans ATCC 10231, B. subtilis ATCC 6633, E. coli ATCC 25922 and S. aureus ATCC 25923. 3-(4-aminobenzoethynyl)-2-(thiophen-2-yl) benzo[b]thiophene (12E), 3-ethynyl-2-(thiophen-2-yl) benzo[b]thiophene (12L) and 3-(2-aminobenzoethynyl)-2-(thiophen-2-yl) benzo[b]thiophene (12J) displayed high antibacterial activity against S. aureus. Further, 3-iodo-2-(thiophen-2-yl) benzo[b]thiophene (10) and 3-(trimethylsilylethynyl)-2-(thiophen-2-yl) benzo[b] thiophene (12K) were found to have potentials to be used as antifungal agents against current fungal diseases. Novel 3-(1H-indole-2-yl)-2-(thiophen-2-yl) benzo[b] thiophene (16) and 3-(4-aminobenzoethynyl)-2-(thiophen-2-yl) benzo[b] thiophene (12E) also showed quite high antioxidant capacities with TEAC values of 2.5 and 1.1, respectively; which surpassed the antioxidant capacity of an universally accepted reference of trolox. Benzothiophene derivatives were synthesized regioselectively using coupling reactions and electrophilic cyclization reactions. Antimicrobial properties of the compounds were tested against four indicator microorganisms, and a few displayed high antibacterial activity against S. aureus. 3-(1H-indole-2-yl)-2-(thiophen-2-yl)benzo[b]thiophene (16) and 3-(4-aminobenzoethynyl)-2-(thiophen-2-yl)benzo[b]thiophene (12E) showed high antioxidant capacities which are better than the reference of trolox.
Synthesis and Biological Properties of Novel 1-Methyl Hydrazine Analogues
(Tubitak Scientific & Technological Research Council Turkey, 2018) Kivrak, Arif; Yilmaz, Can; Konus, Metin; Koca, Halil; Aydemir, Selahattin; Oagaz, Jeger Ali
1-Methyl-2-(2-(prop-2-yn-1-yloxy)benzylidene)hydrazine analogues were readily prepared in good yields by the reaction of 2-(prop-2-yn-1-yloxy)benzaldehydes and methyl hydrazine. The reaction tolerates a variety of substituents on the 2-hydroxybenzaldehyde to form nitro-, halo-, methoxy-, and naphthyl-substituted 1-methyl-2-(2-(prop-2-yn-1-yloxy)benzylidene)hydrazines. The in vitro antioxidant capacity measurements revealed that among all the analyzed hydrazine analogues that surpassed the Trolox standard, 1-(2-(but-3-ynyl)-5-nitrobenzylidene)-2-methylhydrazine had the maximum value, which was approximately 1.7 times that of Trolox.
Synthesis and Evaluation of Antioxidant, Antimicrobial and Anticancer Properties of 2-(prop Derivatives
(Bentham Science Publ Ltd, 2019) Konus, Metin; Aydemir, Selahattin; Yilmaz, Can; Kivrak, Arif; Kizildogan, Aslihan Kurt; Arpaci, Pembegul Uyar
5-bromo-2-(prop-2-yn-1-yloxy)benzaldehyde (compound 3) and 3,5-di-tert-butyl-2-(prop-2-yn-1-yloxy)benzaldehyde (compound 5) were synthesized via nucleophilic substitution reactions. Compound 5 showed higher antioxidant capacity with respect to compound 3 in all the four different antioxidant activity methods used. Moreover, in phosphomolybdenum assay, compound 5, with 1.1 proportion value, showed almost the same total antioxidant capacity compared to universal trolox standard. Furthermore, Broth microdilution method and agar disc diffusion tests demonstrated that the same compound also exhibited good antibacterial activity towards the bacteria Bacillus subtilis. Finally, both of the benzaldehyde compounds showed high antifungal activity against Aspergillus niger. In this study, compound 5 (IC50: 54.3 mu g/ml) showed significant cytotoxic activity against breast adenocarcinoma cell line MCF-7 with respect to compound 3 (IC50: 173.4 mu g/ml).
Synthesis of Ethynyl-Thiophene Derivatives, Antioxidant Properties and Adme Analysis
(Wiley-v C H verlag Gmbh, 2022) Konus, Metin; Algso, Muheb; Yilmaz, Can; Khorsheed, Bahzad Ahmed; Koroglu, Asli; Cetin, Dogan; Kivrak, Arif
Herein, novel alkyne based organic compounds, 2-((2-(methylthio)phenyl)ethynyl)thiophene (MAT) and 2-ethynyl-3-(phenylethynyl)thiophene (DAT), were designed and synthesized via Pd-catalyst cross-coupling reactions. The isolated yields of MAT and DAT were obtained as 77 % and 96 %, respectively. After chemical characterization, radical scavenging activities and reduction power capacities of them were determined by DPPH, TEAC, phosphomolybdenum and reducing power methods. MAT showed higher radical scavenging activities than DAT, and comparable with the standard. Moreover, basic ADME properties were calculated in silico. Both of the newly synthesized derivatives were reported with the same moderate to good drug score of 0.42; and, having potential to pass through BBB and GI with no appointed toxic effects.
Synthesis, Biological Evaluation and Molecular Docking of Novel Thiophene-Based Indole Derivatives as Potential Antibacterial, Gst Inhibitor and Apoptotic Anticancer Agents
(Wiley-v C H verlag Gmbh, 2020) Konus, Metin; Cetin, Dogan; Yilmaz, Can; Arslan, Sevki; Mutlu, Dogukan; Kurt-Kizildogan, Aslihan; Kivrak, Arif
Heteroaromatic indoles play a leading role in the development of pharmaceutical, medical, chemical and agricultural fields due to their structural properties. In this study, it was first time that biological properties of (antioxidant, antimicrobial, cytotoxic and apoptotis-induced anticancer) 3-(5-bromothiophen-2-yl)-1-ethyl-2-phenyl-1H-indole 4 and 3-([2,2 '-bithiophen]-5-yl)-1-ethyl-2-phenyl-1H-indole 5 were described. According to the overall results, while 4 did not show any significant cytotoxic, antioxidant and antimicrobial activities, 5 showed high reducing activity and very strong antibacterial activity against Enterococcus faecalis. Furthermore, 5 showed dose-dependent cytotoxic effect in all tested cell lines. The EC50 values of the 5 were found to be 16 mu M for CaCo-2, 29 mu M for LnCaP, 14 mu M for MDA-MB231, 21 mu M for HepG2 and 87 mu M for HEK293 cells, respectively. 5 also caused induction of apoptosis and promising glutathione S-transferase (GST) enzyme inhibition in HepG2 cells. Consequently, 5 could be also considered as a promising medical agent in cancer treatment.
Synthesis, Cytotoxicity, Antioxidant and Antimicrobial Activity of Indole Based Novel Small Molecules
(Bentham Science Publ Ltd, 2021) Kurt-Kizildogan, Aslihan; Otur, Cigdem; Yilmaz, Can; Arslan, Sevki; Mutlu, Dogukan; Kivrak, Arif; Konus, Metin
Aims: In this study experiments were carried out to explore antioxidant, antimicrobial, cytotoxic properties of novel indole derivative 1-ethyl-2-phenyl-3-phenylethyl-3-thiophen-2-yl-1Hindole (EPI) together with its effect on glutathione S-transferases (GST) activities in human liver carcinoma (HepG2) cells. Background: Indoles probably represent one of the most important heterocyclic structures that have been attracting the interest of many scientists in drug discovery. Objective: The present study was carried out to explore antioxidant, antimicrobial, cytotoxic properties of novel indole derivative 1-ethyl-2-phenyl-3-phenylethyl-3-thiophen-2-yl-1H-indole (EPI) and its effect on glutathione S-transferases (GST) activities in human liver carcinoma (HepG2) cells. Materials and Methods: Pd-catalyst Sonogashira coupling reactions, MTT Assay, Antioxidant capacity test, Antimicrobial test, GST enzyme activity test Results: 1-ethyl-2-phenyl-3-(phenylethynyl)-1H-indole had antioxidant and antimicrobial properties. It displayed significant induction in glutathione S-transferases (GST) enzyme activity in human liver cancer cell lines (HepG2), but cytotoxic effect on all tested cancer cell lines could not be observed. Conclusion: All of these results showed that 1-ethyl-2-phenyl-3-(phenylethynyl)-1H-indole had antioxidant and antimicrobial properties without cytotoxic effect, which could make it a promising active component with further studies..
A Thiophene Derivative, 2-Bromo Has Effective Anticancer Potential With Other Biological Properties
(Wiley-v C H verlag Gmbh, 2022) Yilmaz, Can; Pirdawid, Ahmed Othman; Babat, Ceylan Fidan; Konus, Metin; Cetin, Dogan; Kivrak, Arif; Kizildogan, Aslihan Kurt
Thiophene derivatives are studied intensively due to their anticancer, antimicrobial, antioxidant and some other clinically important properties. In this study, the biological properties of a new thiophene derivative, so called BMPT, with a moderate drug score of 0.29 were tested. BMPT showed selective cytotoxicity for LnCap, HepG2 and Caco-2 cancer cell lines with EC50 values of 138.573 mu M, 185.931 mu M, and 108.657 mu M, respectively, but not on the control cell line HEK293. The increased expressions were detected for caspase3, caspase8, caspase9 and Bax; but Bcl-2 expressions were decreased at cancer cell lines. BMPT decreased the total thiol content and total GST activities at HepG2 47 % and 40 %, respectively, and, molecular docking supported inhibitory models for GSTP1-1, GSTA1-1 and GSTM2-2 were mixed, uncompetitive and uncompetitive, respectively. BMPT also showed potent antibacterial activity against Staphylococcus aureus. Related with its selective inhibition on GST activities, BMPT is proposed to have significant apoptotic effect leaded by changes, especially, in caspase 3, Bcl-2 and Bax expressions.