Antikanser Aktivite Gösterebilecek Yeni Heterohalkalı Bileşiklerin Sentezlenmesi Ve Karakterizasyonu

Abstract

Son yıllarda kanser hastalığı üzerinde yapılan çalışmaların sayısı oldukça artmaktadır. Çeşitli kanser türlerine karşı etkili olabilecek anti-kanser ilaçlarının yenilerinin elde edilmesi için çeşitli çalışmalar yapılmaktadır. Bu çalışmada anti-kanser aktivite gösterebilecek yeni bisiklik schiff bazı türevleri sentezlenmiş ve sentezlenen yeni bileşiklerin yapıları IR, ¹H-NMR, ¹³C-NMR, GC-MS gibi spektroskopik yöntemlerle yapıları karakterize edilmiştir.

Keywords

• Anti-kanser aktivite,Anti-kanser ilaçlar,Heck reaksiyonları,Heterohalkalı bileşikler

References

1. 1. Dang, C. V. (2018). Convergence to Cure Cancer through Research. Cancer Res, 78 (1), 3-4.
2. 2. Hait, W. N. (2011). Forty Years of Translational Cancer Research. Cancer Discov, 1 (7), 627-627.
3. 3. Balaraman, S., Nayak, N., Subbiah, M. ve Elango, K. P. (2018). Synthesis and antiviral study of novel 4-(2-(6-amino-4-oxo-4,5-dihydro-1H-pyrrolo[2,3-d]pyrimidin-3-yl)ethyl)benzamide derivatives. Med Chem Res 27 (11-12), 2538-2546.
4. 4. Gujarati, N. A., Zeng, L. L., Gupta, P., Chen, Z. S. ve Korlipara, V. L. (2017). Design, synthesis and biological evaluation of benzamide and phenyltetrazole derivatives with amide and urea linkers as BCRP inhibitors. Bioorg Med Chem Lett, 27 (20), 4698-4704.
5. 5. Kaur, A., Pathak, D. P., Sharma, V., Narasimhan, B., Sharma, P., Mathur, R. ve Wakode, S. (2018). Synthesis, biological evaluation and docking study of N-(2-(3,4,5-trimethoxybenzyl)benzoxazole-5-yl) benzamide derivatives as selective COX-2 inhibitor and anti-inflammatory agents. Bioorg Chem, 81, 191-202.
6. 6. Lu, K., Cai, L. D., Zhang, X., Wu, G. D., Xu, C. J., Zhao, Y. F. ve Gong, P. (2018). Design, synthesis, and biological evaluation of novel substituted benzamide derivatives bearing a 1,2,3-triazole moiety as potent human dihydroorotate dehydrogenase inhibitors. Bioorg Chem, 76, 528-537.
7. 7. Perin, N., Roskaric, P., Sovic, I., Bocek, I., Starcevic, K., Hranjec, M. ve Vianello, R. (2018). Amino-Substituted Benzamide Derivatives as Promising Antioxidant Agents: A Combined Experimental and Computational Study. Chem Res Toxicol, 31 (9), 974-984.
8. 8. Thirumurugan, K., Lakshmanan, S., Govindaraj, D., Prabu, D. S. D., Ramalakshmi, N. ve Antony, S. A. (2018). Design, synthesis and anti-inflammatory activity of pyrimidine scaffold benzamide derivatives as epidermal growth factor receptor tyrosine kinase inhibitors. J Mol Struct, 1171, 541-550.

9. 9. Vandyck, K., Rombouts, G., Stoops, B., Tahri, A., Vos, A., Verschueren, W., Wu, Y. M., Yang, J. M., Hou, F. L., Huang, B., Vergauwen, K., Dehertogh, P., Berke, J. M. ve Raboisson, P. (2018). Synthesis and Evaluation of N-Phenyl-3-sulfamoyl-benzamide Derivatives as Capsid Assembly Modulators Inhibiting Hepatitis B Virus (HBV). J Med Chem 61 (14), 6247-6260.
10. 10. Wei, M. M., Peng, X., Xing, L., Dai, Y., Huang, R. M., Geng, M. Y., Zhang, A., Ai, J. ve Song, Z. L. (2018). Design, synthesis and biological evaluation of a series of novel 2-benzamide-4-(6-oxy-N-methyl-l-naphthamide)-pyridine derivatives as potent fibroblast growth factor receptor (FGFR) inhibitors. Eur J Med Chem, 154, 9-28.
11. 11. Creaven, B. S., Duff, B., Egan, D. A., Kavanagh, K., Rosair, G., Thangella, V. R. ve Walsh, M. (2010). Anticancer and antifungal activity of copper(II) complexes of quinolin-2(1H)-one-derived Schiff bases. Inorg Chim Acta, 363 (14), 4048-4058.
12. 12. Ghorab, M. M., Shaaban, M. A., Refaat, H. M., Heiba, H. I. ve Ibrahim, S. S. (2012). Anticancer and radiosensitizing evaluation of some new pyranothiazole-Schiff bases bearing the biologically active sulfonamide moiety. Eur J Med Chem, 53, 403-407.
13. 13. Obeid, A., El-Shekeil, A., Al-Aghbari, S., Al-Shabi, J. (2012). Anticancer, DNA cleavage, and antimicrobial activity studies of some new Schiff-base titanium(IV) complexes. J Coord Chem, 65 (15), 2762-2770.
14. 14. Pignatello, R., Panico, A., Mazzone, P., Pinizzotto, M. R., Garozzo, A. ve Furneri, P. M. (1994). Schiff-Bases of N-Hydroxy-N'-Aminoguanidines as Antiviral, Antibacterial and Anticancer Agents. Eur J Med Chem, 29 (10), 781-785.
15. 15. Shukla, S., Srivastava, R. S., Shrivastava, S. K., Sodhi, A. ve Kumar, P. (2013). Synthesis, characterization, in vitro anticancer activity, and docking of Schiff bases of 4-amino-1,2-naphthoquinone. Med Chem Res, 22 (4), 1604-1617.
16. 16. Sondhi, S. M., Arya, S., Rani, R., Kumar, N. ve Roy, P. (2012). Synthesis, anti-inflammatory and anticancer activity evaluation of some mono- and bis-Schiff's bases. Med Chem Res. 21 (11), 3620-3628.
17. 17. Tabassum, S., Amir, S., Arjmand, F., Pettinari, C., Marchetti, F., Masciocchi, N., Lupidi, G. ve Pettinari, R. (2013). Mixed-ligand Cu(II)-vanillin Schiff base complexes; effect of coligands on their DNA binding, DNA cleavage, SOD mimetic and anticancer activity. Eur J Med Chem, 60, 216-232.
18. 18. Berlinck, R. G. S., Britton, R., Piers, E., Lim, L., Roberge, M., da Rocha, R. M. ve Andersen, R. J. (1998). Granulatimide and isogranulatimide, aromatic alkaloids with G2 checkpoint inhibition activity isolated from the Brazilian ascidian Didemnum granulatum: Structure elucidation and synthesis. J Org Chem, 63 (26), 9850-9856.
19. 19. Lavrard, H., Rodriguez, F. ve Delfourne, E. (2014). Design of granulatimide and isogranulatimide analogues as potential Chk1 inhibitors: Study of amino-platforms for their synthesis. Bioorgan Med Chem, 22 (17), 4961-4967.
20. 20. Loubinoux, B., Gerardin, P., Kunz, W. ve Herzog, J. (1991). Activity of Fumaramidmycin Mimics against Oomycetes. Pestic Sci, 33 (3), 263-269.
21. 21. Moreau, P., Anizon, F., Sancelme, M., Prudhomme, M., Bailly, C., Carrasco, C., Ollier, M., Severe, D., Riou, J. F., Fabbro, D., Meyer, T. ve Aubertin, A. M. (1998). Syntheses and biological evaluation of indolocarbazoles, analogues of rebeccamycin, modified at the imide heterocycle. J Med Chem, 41 (10), 1631-1640.
22. 22. Moreau, P., Anizon, F., Sancelme, M., Prudhomme, M., Severe, D., Riou, J. F., Goossens, J. F., Henichart, J. P., Bailly, C., Labourier, E., Tazzi, J., Fabbro, D., Meyer, T. ve Aubertin, A. M. (1999). Synthesis, mode of action, and biological activities of rebeccamycin bromo derivatives. J Med Chem, 42 (10), 1816-1822.
23. 23. Browne, S. G. (1960). Cantharidin Poisoning Due to a "Blister Beetle". Br Med J, 2 (5208), 1290-1.
24. 24. Feng, S., Zhu, J., Xia, K., Yu, W., Wang, Y., Wang, J., Li, F., Yang, Z., Yang, X., Liu, B., Tao, H. ve Liang, C. (2018). Cantharidin Inhibits Anti-Apoptotic Bcl-2 Family Proteins and Induces Apoptosis in Human Osteosarcoma Cell Lines MG-63 and MNNG/HOS via Mitochondria-Dependent Pathway. Med Sci Monit, 24, 6742-6749.
25. 25. Liu, Y. P., Li, L., Xu, L., Dai, E. N. ve Chen, W. D. (2018). Cantharidin suppresses cell growth and migration, and activates autophagy in human non-small cell lung cancer cells. Oncol Lett, 15 (5), 6527-6532.
26. 26. Mu, Z. ve Sun, Q. (2018). Cantharidin inhibits melanoma cell proliferation via the miR21mediated PTEN pathway. Mol Med Rep, 18 (5), 4603-4610.
27. 27. Wang, G., Dong, J. ve Deng, L. (2018). Overview of Cantharidin and its Analogues. Curr Med Chem, 25 (17), 2034-2044.
28. 28. Wang, W. J., Wu, M. Y.,Shen, M., Zhi, Q., Liu, Z. Y., Gong, F. R., Tao, M. ve Li, W. (2015). Cantharidin and norcantharidin impair stemness of pancreatic cancer cells by repressing the beta-catenin pathway and strengthen the cytotoxicity of gemcitabine and erlotinib. Int J Oncol, 47 (5), 1912-22.
29. 29. Li, C. C., Yu, F. S., Fan, M. J., Chen, Y. Y., Lien, J. C., Chou, Y. C., Lu, H. F., Tang, N. Y., Peng, S. F., Huang, W. W. ve Chung, J. G. (2017). Anticancer effects of cantharidin in A431 human skin cancer (Epidermoid carcinoma) cells in vitro and in vivo. Environ Toxicol, 32 (3), 723-738.
30. 30. Gul, M., Kulu, I., Gunkara, O. T. ve Ocal, N. (2013). Reductive Heck Reactions and [3+2] Cycloadditions of Unsaturated N,N'-Bistricyclic Imides. Acta Chim Slov, 60 (1), 87-94.
31. 31. Gunkara, O. T., Kulu, I. ve Ocal, N. (2015). Aryl- and Heteroaryl Substituted Tandospirones as Possible Antidepressant Drugs. Mini-Rev Med Chem, 15 (9), 789-796.
32. 32. Gunkara, O. T., Kulu, I., Ocal, N. ve Kaufmann, D. E. (2010). Synthesis of arylated norbornyl amino acid esters. Monatsh Chem, 141 (11), 1237-1243.
33. 33. Gunkara, O. T. ve Ocal, N. (2015). Hydroarylation Reactions of N-Substituted Tricyclic Imides. Mini-Rev Org Chem, 12 (5), 424-434.
34. 34. Niwayama, S., Cho, H., Zabet-Moghaddam, M. ve Whittlesey, B. R. (2010). Remote exo/endo selectivity in selective monohydrolysis of dialkyl bicyclo[2.2.1]heptane-2,3-dicarboxylate derivatives. J Org Chem, 75 (11), 3775-80.
35. 35. Kas'yan, L. I., Tarabara, I. N., Bondarenko, Y. S., Shishkina, S. V., Shishkin, O. V. ve Musatov, V. I. (2005). Structure and reactivity of bicyclo[2.2.1]hept-2-ene-endo-5,endo-6-dicarboxylic (endic) acid hydrazide. Russ J Org Chem+, 41 (8), 1122-1131.