Araştırma Makalesi
Investigation of anticancer and antimicrobial properties of fluorinated salicylaldimine’s Florlu salisilaldiminlerin antikanser ve antimikrobiyal özelliklerinin araştırılması
Öz
Bioactive molecules with higher activation power are now needed instead of organic compounds that are widely used against drug resistance that threatens human health. The development of Schiff base (SB) compounds supported by the unique properties of the fluorine atom may increase the chances of curing of drug-resistant lung cancer and bacterial infections. A series of fluorinated salicylaldimine SB ligands (C1-10) were synthesized. Their anticancer effects on the A549 human lung carcinoma cell line and antibacterial effects on Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa were tested by MTT (3-(4,5-dimethylthi azol-2-yl)-2, 5-diphenyltetrazolium bromide) assay. CFSE (5(6)-Carboxyfluoresceindiacetate N-succinimidyl ester) method was used to determine the proliferative indexes (PI) of the compounds on A549 cells. The apoptosis-induce capabilities of the compounds were determined by active caspase-3 analysis and mitochondrial membrane potential analysis using rhodamine123. Morphological changes indicating apoptosis in the cells were determined by standard Hematoxylin and eosin, Giemsa and Papanicolaou staining protocols. Three fluorine-bearing (F2,4,5-SAL) SB ligands (C7) showed stronger cytotoxic activity than DOX on A549 cells (1.4 to 1.9 µM, respectively). The antiproliferative effects of the compounds were weaker than DOX. Mitochondrial membrane potential, active caspase analysis together with cell morphology analyses proved that cell death occurred by induction of apoptosis. No significant antibacterial effects of the compounds were found on the bacterial strains.
Anahtar Kelimeler
Schiff base salicylaldimines fluorıne anticancer antibacterial
Destekleyen Kurum
HUBAK
Proje Numarası
20160
Teşekkür
This study supported by Harran University Scientific Research Project Coordination Unit (Project no: 20160). Providing the supply of chemical compounds, Prof. Dr. Thank you Veli KASUMOV.
Kaynakça
- Chabner BA, Roberts TG Jr. Chemotherapy and the war on cancer. Nat Rev Cancer.2005;5: 65–72.
- Kamb A, Wee S, Lengauer C.Why is cancer drug discovery so difficult? Nat Rev Drug Disc. 2007; 6: 115–120.
- Shilpa BS, Padmamma S, Kumara AT. Mapping of scientific articles on Leukemia: A scientometric study. Libr Philos Pract. 2019; 1: 1-24.
- Aktimur SH, Gunes AK, Akidan O. Efficacy of the Combination of Venetoclax and Azacitidine in Elderly of Frail Relapsed/Refractory Patients with Acute Myeloid Leukemia, First Multi-Institutional Real World Experience from Türkiye. J Hematol Oncol. 2020; 31(4): 213.
- Kankala RK, Liu CG, Yang DY. Ultrasmall platinum nanoparticles enable deep tumor penetration and synergistic therapeutic abilities through free radical species-assisted catalysis to combat cancer multidrug resistance. Chem Eng J. 2020;383: 123.
- Sonbol, H., Ameen, F., AlYahya, S., Almansob, A., & Alwakeel, S. Padina Boryana mediated green synthesis of crystalline palladium nanoparticles as potential nanodrug against multidrug-resistant bacteria and cancer cells. Scientific reports. 2021; 11(1), 1-19.
- Magiorakos, A. P., Srinivasan, A., Carey, R. B., Carmeli, Y., Falagas, M. E., Giske, C. G., Monnet, D. L. Multidrug-resistant, extensively drug-resistant and pan drug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clinical microbiology and infection. 2012;18(3), 268-281.
- Moitra K. Overcoming Multidrug Resistance in Cancer Stem Cells. Biomed Res Int. 2015:635745.
- Wang, X., Zhang, H., & Chen, X. Drug resistance and combating drug resistance in cancer. Cancer Drug Resistance. 2019; 2(2), 141.
- Orsi, G. B., Falcone, M., & Venditti, M. (2011). Surveillance and management of multidrug-resistant microorganisms. Expert Review of Anti-Infective Therapy. 2019; 9(8), 653-679.
- Peraman, R., Sure, S. K., Dusthackeer, V. N., Chilamakuru, N. B., Yiragamreddy, P. R., Pokuri, C.,et.al. Insights on recent approaches in drug discovery strategies and untapped drug targets against drug resistance. Future Journal of Pharmaceutical Sciences. 2021; 7(1), 1-25.
- WC Soo, V., Kwan, B. W., Quezada, H., Castillo-Juárez, I., Pérez-Eretza, B., Julieta García-Contreras, S., García-Contreras, R. Repurposing of anticancer drugs for the treatment of bacterial infections. Current topics in medicinal chemistry. 2017; 17(10), 1157-1176.
- Can, G. Side effects of antineoplastic drugs and nursing approaches. Journal of Education and Research in Nursing. 2005; 2(2), 8-15.
- Majolo, F., Delwing, L. K. D. O. B., Marmitt, D. J., Bustamante-Filho, I. C., & Goettert, M. I. Medicinal plants and bioactive natural compounds for cancer treatment: Important advances for drug discovery. Phytochemistry Letters. 2019; 31, 196-207.
- Temel, M. K. The development of cytotoxic chemotherapeutics in the twentieth century. Turkish Journal of Oncology. 2015; 30(2).
- Bukowski, K., Kciuk, M., & Kontek, R. Mechanisms of multidrug resistance in cancer chemotherapy. International journal of molecular sciences. 2020; 21(9), 3233.
- Uddin, M. N., Ahmed, S. S., & Alam, S. R. Biomedical applications of Schiff base metal complexes. Journal of Coordination Chemistry. 2020; 73(23), 3109-3149.
- Matela, G. Schiff bases and complexes: a review on anti-cancer activity. Anti-Cancer Agents in Medicinal Chemistry. 2020; 20(16), 1908-1917.
- Al-Harthy, T., Zoghaib, W., & Abdel-Jalil, R.Importance of fluorine in benzazole compounds. Molecules. 2020; 25(20), 4677.
- Inoue, M., Sumii, Y., & Shibata, N. Contribution of organofluorine compounds to pharmaceuticals. ACS omega. 2020;5(19), 10633-10640.
- Bildik A, Bayar İ. Kanserde apoptotik Yolakların İnhibisyonu. Turkiye Klinikleri J Vet Sci. 2018;9(2):42-51.
- Kaya C, Çalışkan Y, Yönden Z. Apoptozis. The Medical Journal of Mustafa Kemal University. 2012; 3(11); 26-37.
- Atagün G, Zafer, E, Gürkanlı İ. Apoptoziste mitokondrinin rolü. Türk Bilimsel Derlemeler Dergisi. 2011;4(2): 9-53.
- Dağdeviren T. Programlı hücre ölümü; Apoptoz. Gaziosmanpaşa Üniversitesi Tıp Fakültesi Dergisi. 2021; 3(3), 120-135.
- Coşkun G, Özgür H. Apoptoz ve nekrozun moleküler mekanizması. Arşiv Kaynak Tarama Dergisi. 2012; 20(3): 145-158.
- Berrouet C, Dorilas N, Rejniak K A, Tuncer N. Comparison of drug inhibitory effects (IC 50) in monolayer and spheroid cultures. Bulletin of Mathematical Biology,2020; 82(6) 68.
- Elias J M. Cell proliferation indexes: a biomarker in solid tumors. Biotechnic & histochemistry, 1997; 72(2): 78-85.
- Schwarz S, Silley P, Simjee S, Woodford N, van Duijkeren E, Johnson A P., et al. (Assessing the antimicrobial susceptibility of bacteria obtained from animals. Journal of antimicrobial chemotherapy. 2010; 65(4): 601-604.
- Rice, L. B. Unmet medical needs in antibacterial therapy. Biochemical pharmacology. 2006; 71(7), 991-995.
- Fekri R, Salehi M, Asadi A. Synthesis, characterization, anticancer and antibacterial evaluation of Schiff base ligands derived from hydrazone and their transition metal complexes. Inorganica Chim Acta. 2019; 484: 245-254.
- Kumar, A., Chakma, U., Chandra, A., Howlader, D., Akash, S., Kobir, M., et.al. Modified D-glucofuranose computationally screening for inhibitor of breast cancer and triple breast cancer: Chemical descriptor, molecular docking, molecular dynamics, and QSAR. Journal of the Chilean Chemical Society. 2022; 67(3), 5623-5635.
- Housman, G., Byler, S., Heerboth, S., Lapinska, K., Longacre, M., Snyder, N., & et.al. Drug resistance in cancer: an overview. Cancers. 2014; 6(3), 1769-1792.
- Strunecká, A., Patočka, J., & Connett, P.Fluorine in medicine. J Appl Biomed. 2004; 2, 141-150.
- Kurtdede, E. Türkiye’de florozis sorunu ve florun biyokimyasal etkileşimi. Atatürk Üniversitesi Veteriner Bilimleri Dergisi. 2017; 2(3), 320-326.
- Chen, S., Liu, X., Ge, X., Wang, Q., Xie, Y., Hao, Y., et.al. Lysosome-targeted iridium (III) compounds with pyridine-triphenylamine Schiff base ligands: Syntheses, antitumor applications and mechanisms. Inorganic Chemistry Frontiers. 2020; 7(1), 91-100.
- Gupta, D., & Jain, D. K. Synthesis, antifungal and antibacterial activity of novel 1, 2, 4-triazole derivatives. Journal of advanced pharmaceutical technology & research. 2015; 6(3), 141.
- Avila-Sorrosa, A., Bando-Vázquez, A. Y., Alvarez-Alvarez, V., Suarez-Contreras, E., Nieto-Meneses, R., Nogueda-Torres, B., et. al. Synthesis, characterization and preliminary in vitro trypanocidal activity of N-arylfluorinated hydroxylated-Schiff bases. Journal of Molecular Structure. 2020; 1218, 128520.
- Wu, R., Bi, C., Zhang, X., Zong, Z., Fan, C., Zhang, X., et.al. Syntheses, crystal structure and biological evaluation of three novel Cu (II) complexes with Schiff base derived from fluorinated amino acid and Salicylaldehyde. Applied Organometallic Chemistry. 2020; 34(1), e5264.
- Würtenberger, I., Follia, V., Lerch, F., Cwikla, C., Fahrner, N., Kalchschmidt, C., et. Al. Fluorinated Fe (III) salophene complexes: optimization of tumor cell-specific activity and utilization of fluorine labeling for in vitro analysis. Journal of Medicinal Chemistry. 2015; 58(2), 588-597.
- Zeng, L., Deng, Y., Weng, L., Yang, Z., Chen, H., Liu, Q. Synthesis and Anti-Tumor Activities of Fluoride-Containing Gossypol Derivatives Compounds. Natural Science. 2017;9(9), 312-318.
- Mahal, A., Wu, P., Jiang, Z. H., & Wei, X. Schiff bases of tetrahydro curcumin as potential anticancer agents. Chemistry Select. 2019; 4(1), 366-369.
- Sak, Z. H. A., Süzergöz, F., Kasumov, V. T., Gürol, A. O. Anticancer Properties of Fluorinated Aminophenylhydrazines on A549 Lung Carcinoma Cell Line. Iranian Journal of Public Health. 2021; 50(3), 550-556.
- Gurol, A. O., Kasim, V., Suzergoz, F. Antiproliferative effects of fluorine substitute 3, 5-di-tert-butylphenol bearing Schiff bases using CFSE-based cell proliferation assay. Current Science. 2017;619-624.
- Li, L., Wang, S., & Zhou, W.Balance. Cell Apoptosis and Pyroptosis of Caspase-3-Activating Chemotherapy for Better Antitumor Therapy. Cancers. 2022; 15(1), 26.
- Xia, Y., Liu, X., Zhang, L., Zhang, J., Li, C., Zhang, N., Li, Y. A new Schiff base coordinated copper (II) compound induces apoptosis and inhibits tumor growth in gastric cancer. Cancer Cell International. 2019; 19, 1-11.
- Avila-Sorrosa, A., Hernández-González, J. I., Reyes-Arellano, A., Toscano, R. A., Reyes-Martínez, R., Pioquinto-Mendoza, J. R., et.al. Synthesis, structural characterization and biological activity of fluorinated Schiff-bases of the type [C6H4-1-(OH)-3-(CHNArF)]. Journal of Molecular Structure. 2015; 1085, 249-257.
- Carreño A, Rodríguez L, Páez-Hernández D, Martin-Trasanco R, Zúñiga C, Oyarzún DP, et.al. Two New Fluorinated Phenol Derivatives Pyridine Schiff Bases: Synthesis, Spectral, Theoretical Characterization, Inclusion in Epichlorohydrin-β-Cyclodextrin Polymer, and Antifungal Effect. Front Chem.2018;30; 6:312.
- Shanmugam M, Narayanan K, Mahalakshmi M, Kabilan S, Chidambaranathan V.Synthesis, characterization and biological studies of some novel 3-fluorosalicylaldehyde based amine derivatives. Spectrochim Acta A Mol Biomol Spectrosc. 2013; 116:394-400.
Yıl 2023,
Cilt: 12 Sayı: 4, 54 - 62, 28.12.2023
Öz
Proje Numarası
20160
Kaynakça
- Chabner BA, Roberts TG Jr. Chemotherapy and the war on cancer. Nat Rev Cancer.2005;5: 65–72.
- Kamb A, Wee S, Lengauer C.Why is cancer drug discovery so difficult? Nat Rev Drug Disc. 2007; 6: 115–120.
- Shilpa BS, Padmamma S, Kumara AT. Mapping of scientific articles on Leukemia: A scientometric study. Libr Philos Pract. 2019; 1: 1-24.
- Aktimur SH, Gunes AK, Akidan O. Efficacy of the Combination of Venetoclax and Azacitidine in Elderly of Frail Relapsed/Refractory Patients with Acute Myeloid Leukemia, First Multi-Institutional Real World Experience from Türkiye. J Hematol Oncol. 2020; 31(4): 213.
- Kankala RK, Liu CG, Yang DY. Ultrasmall platinum nanoparticles enable deep tumor penetration and synergistic therapeutic abilities through free radical species-assisted catalysis to combat cancer multidrug resistance. Chem Eng J. 2020;383: 123.
- Sonbol, H., Ameen, F., AlYahya, S., Almansob, A., & Alwakeel, S. Padina Boryana mediated green synthesis of crystalline palladium nanoparticles as potential nanodrug against multidrug-resistant bacteria and cancer cells. Scientific reports. 2021; 11(1), 1-19.
- Magiorakos, A. P., Srinivasan, A., Carey, R. B., Carmeli, Y., Falagas, M. E., Giske, C. G., Monnet, D. L. Multidrug-resistant, extensively drug-resistant and pan drug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clinical microbiology and infection. 2012;18(3), 268-281.
- Moitra K. Overcoming Multidrug Resistance in Cancer Stem Cells. Biomed Res Int. 2015:635745.
- Wang, X., Zhang, H., & Chen, X. Drug resistance and combating drug resistance in cancer. Cancer Drug Resistance. 2019; 2(2), 141.
- Orsi, G. B., Falcone, M., & Venditti, M. (2011). Surveillance and management of multidrug-resistant microorganisms. Expert Review of Anti-Infective Therapy. 2019; 9(8), 653-679.
- Peraman, R., Sure, S. K., Dusthackeer, V. N., Chilamakuru, N. B., Yiragamreddy, P. R., Pokuri, C.,et.al. Insights on recent approaches in drug discovery strategies and untapped drug targets against drug resistance. Future Journal of Pharmaceutical Sciences. 2021; 7(1), 1-25.
- WC Soo, V., Kwan, B. W., Quezada, H., Castillo-Juárez, I., Pérez-Eretza, B., Julieta García-Contreras, S., García-Contreras, R. Repurposing of anticancer drugs for the treatment of bacterial infections. Current topics in medicinal chemistry. 2017; 17(10), 1157-1176.
- Can, G. Side effects of antineoplastic drugs and nursing approaches. Journal of Education and Research in Nursing. 2005; 2(2), 8-15.
- Majolo, F., Delwing, L. K. D. O. B., Marmitt, D. J., Bustamante-Filho, I. C., & Goettert, M. I. Medicinal plants and bioactive natural compounds for cancer treatment: Important advances for drug discovery. Phytochemistry Letters. 2019; 31, 196-207.
- Temel, M. K. The development of cytotoxic chemotherapeutics in the twentieth century. Turkish Journal of Oncology. 2015; 30(2).
- Bukowski, K., Kciuk, M., & Kontek, R. Mechanisms of multidrug resistance in cancer chemotherapy. International journal of molecular sciences. 2020; 21(9), 3233.
- Uddin, M. N., Ahmed, S. S., & Alam, S. R. Biomedical applications of Schiff base metal complexes. Journal of Coordination Chemistry. 2020; 73(23), 3109-3149.
- Matela, G. Schiff bases and complexes: a review on anti-cancer activity. Anti-Cancer Agents in Medicinal Chemistry. 2020; 20(16), 1908-1917.
- Al-Harthy, T., Zoghaib, W., & Abdel-Jalil, R.Importance of fluorine in benzazole compounds. Molecules. 2020; 25(20), 4677.
- Inoue, M., Sumii, Y., & Shibata, N. Contribution of organofluorine compounds to pharmaceuticals. ACS omega. 2020;5(19), 10633-10640.
- Bildik A, Bayar İ. Kanserde apoptotik Yolakların İnhibisyonu. Turkiye Klinikleri J Vet Sci. 2018;9(2):42-51.
- Kaya C, Çalışkan Y, Yönden Z. Apoptozis. The Medical Journal of Mustafa Kemal University. 2012; 3(11); 26-37.
- Atagün G, Zafer, E, Gürkanlı İ. Apoptoziste mitokondrinin rolü. Türk Bilimsel Derlemeler Dergisi. 2011;4(2): 9-53.
- Dağdeviren T. Programlı hücre ölümü; Apoptoz. Gaziosmanpaşa Üniversitesi Tıp Fakültesi Dergisi. 2021; 3(3), 120-135.
- Coşkun G, Özgür H. Apoptoz ve nekrozun moleküler mekanizması. Arşiv Kaynak Tarama Dergisi. 2012; 20(3): 145-158.
- Berrouet C, Dorilas N, Rejniak K A, Tuncer N. Comparison of drug inhibitory effects (IC 50) in monolayer and spheroid cultures. Bulletin of Mathematical Biology,2020; 82(6) 68.
- Elias J M. Cell proliferation indexes: a biomarker in solid tumors. Biotechnic & histochemistry, 1997; 72(2): 78-85.
- Schwarz S, Silley P, Simjee S, Woodford N, van Duijkeren E, Johnson A P., et al. (Assessing the antimicrobial susceptibility of bacteria obtained from animals. Journal of antimicrobial chemotherapy. 2010; 65(4): 601-604.
- Rice, L. B. Unmet medical needs in antibacterial therapy. Biochemical pharmacology. 2006; 71(7), 991-995.
- Fekri R, Salehi M, Asadi A. Synthesis, characterization, anticancer and antibacterial evaluation of Schiff base ligands derived from hydrazone and their transition metal complexes. Inorganica Chim Acta. 2019; 484: 245-254.
- Kumar, A., Chakma, U., Chandra, A., Howlader, D., Akash, S., Kobir, M., et.al. Modified D-glucofuranose computationally screening for inhibitor of breast cancer and triple breast cancer: Chemical descriptor, molecular docking, molecular dynamics, and QSAR. Journal of the Chilean Chemical Society. 2022; 67(3), 5623-5635.
- Housman, G., Byler, S., Heerboth, S., Lapinska, K., Longacre, M., Snyder, N., & et.al. Drug resistance in cancer: an overview. Cancers. 2014; 6(3), 1769-1792.
- Strunecká, A., Patočka, J., & Connett, P.Fluorine in medicine. J Appl Biomed. 2004; 2, 141-150.
- Kurtdede, E. Türkiye’de florozis sorunu ve florun biyokimyasal etkileşimi. Atatürk Üniversitesi Veteriner Bilimleri Dergisi. 2017; 2(3), 320-326.
- Chen, S., Liu, X., Ge, X., Wang, Q., Xie, Y., Hao, Y., et.al. Lysosome-targeted iridium (III) compounds with pyridine-triphenylamine Schiff base ligands: Syntheses, antitumor applications and mechanisms. Inorganic Chemistry Frontiers. 2020; 7(1), 91-100.
- Gupta, D., & Jain, D. K. Synthesis, antifungal and antibacterial activity of novel 1, 2, 4-triazole derivatives. Journal of advanced pharmaceutical technology & research. 2015; 6(3), 141.
- Avila-Sorrosa, A., Bando-Vázquez, A. Y., Alvarez-Alvarez, V., Suarez-Contreras, E., Nieto-Meneses, R., Nogueda-Torres, B., et. al. Synthesis, characterization and preliminary in vitro trypanocidal activity of N-arylfluorinated hydroxylated-Schiff bases. Journal of Molecular Structure. 2020; 1218, 128520.
- Wu, R., Bi, C., Zhang, X., Zong, Z., Fan, C., Zhang, X., et.al. Syntheses, crystal structure and biological evaluation of three novel Cu (II) complexes with Schiff base derived from fluorinated amino acid and Salicylaldehyde. Applied Organometallic Chemistry. 2020; 34(1), e5264.
- Würtenberger, I., Follia, V., Lerch, F., Cwikla, C., Fahrner, N., Kalchschmidt, C., et. Al. Fluorinated Fe (III) salophene complexes: optimization of tumor cell-specific activity and utilization of fluorine labeling for in vitro analysis. Journal of Medicinal Chemistry. 2015; 58(2), 588-597.
- Zeng, L., Deng, Y., Weng, L., Yang, Z., Chen, H., Liu, Q. Synthesis and Anti-Tumor Activities of Fluoride-Containing Gossypol Derivatives Compounds. Natural Science. 2017;9(9), 312-318.
- Mahal, A., Wu, P., Jiang, Z. H., & Wei, X. Schiff bases of tetrahydro curcumin as potential anticancer agents. Chemistry Select. 2019; 4(1), 366-369.
- Sak, Z. H. A., Süzergöz, F., Kasumov, V. T., Gürol, A. O. Anticancer Properties of Fluorinated Aminophenylhydrazines on A549 Lung Carcinoma Cell Line. Iranian Journal of Public Health. 2021; 50(3), 550-556.
- Gurol, A. O., Kasim, V., Suzergoz, F. Antiproliferative effects of fluorine substitute 3, 5-di-tert-butylphenol bearing Schiff bases using CFSE-based cell proliferation assay. Current Science. 2017;619-624.
- Li, L., Wang, S., & Zhou, W.Balance. Cell Apoptosis and Pyroptosis of Caspase-3-Activating Chemotherapy for Better Antitumor Therapy. Cancers. 2022; 15(1), 26.
- Xia, Y., Liu, X., Zhang, L., Zhang, J., Li, C., Zhang, N., Li, Y. A new Schiff base coordinated copper (II) compound induces apoptosis and inhibits tumor growth in gastric cancer. Cancer Cell International. 2019; 19, 1-11.
- Avila-Sorrosa, A., Hernández-González, J. I., Reyes-Arellano, A., Toscano, R. A., Reyes-Martínez, R., Pioquinto-Mendoza, J. R., et.al. Synthesis, structural characterization and biological activity of fluorinated Schiff-bases of the type [C6H4-1-(OH)-3-(CHNArF)]. Journal of Molecular Structure. 2015; 1085, 249-257.
- Carreño A, Rodríguez L, Páez-Hernández D, Martin-Trasanco R, Zúñiga C, Oyarzún DP, et.al. Two New Fluorinated Phenol Derivatives Pyridine Schiff Bases: Synthesis, Spectral, Theoretical Characterization, Inclusion in Epichlorohydrin-β-Cyclodextrin Polymer, and Antifungal Effect. Front Chem.2018;30; 6:312.
- Shanmugam M, Narayanan K, Mahalakshmi M, Kabilan S, Chidambaranathan V.Synthesis, characterization and biological studies of some novel 3-fluorosalicylaldehyde based amine derivatives. Spectrochim Acta A Mol Biomol Spectrosc. 2013; 116:394-400.
Toplam 48 adet kaynakça vardır.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Sağlık Kurumları Yönetimi |
| Bölüm | Makaleler |
| Yazarlar | |
| Proje Numarası | 20160 |
| Erken Görünüm Tarihi | 28 Aralık 2023 |
| Yayımlanma Tarihi | 28 Aralık 2023 |
| Yayımlandığı Sayı | Yıl 2023 Cilt: 12 Sayı: 4 |
Kaynak Göster
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