Synthesis and characterizations of novel thiazolyl-thiadiazole derivatives as telomerase activators
Synthesis and characterizations of novel thiazolyl-thiadiazole derivatives as telomerase activators
Pyridine-3/4-thiocarboxamide derivatives were used as starting materials for the synthesis of the targetcompounds. The pyridine-3/4-thiocarboxamide derivatives were reacted with ethyl 2-chloroacetoacetate in ethanol togive the thiazole derivatives (1, 2). The two ethyl thiazole-carboxylate derivatives (1, 2) thus obtained were treated withsodium hydroxide solution and ethanol and converted to carboxylic acids (3, 4). The carboxylic acid derivatives (3, 4)were reacted with thiosemicarbazide in phosphoroxy trichloride and aminothiadiazole rings (5, 6) were formed. Thus,two thiazolyl-thiadiazole amine derivatives (5, 6) were obtained. These two derivatives (5, 6) were converted into twochloroacetamidothiadiazole derivatives (7, 8) by reaction with chloroacetylchloride over the amino group in the presenceof triethylamine in acetone. After all these steps, the starting materials (7, 8) needed to reach the target compoundswere obtained. With the two derivatives (7, 8) obtained in this last step, phenol and thiophenol derivatives were reactedin acetone in the presence of potassium carbonate. The target compounds, thiazolyl-thiadiazole derivatives (TDA1−16),are completely unique and their structure has been elucidated by elemental analysis, IR, NMR, and MS spectral data.After all these synthesis steps, telomerase activity studies were performed on the target compounds obtained. For thispurpose, a PCR ELISA-based TRAP method was used on the heart of zebrafish. According to the enzyme assay results,derivative TDA8 has shown an increase of telomerase enzyme activity.
___
- 1. Daidone, G.; Maggio, B.; Schillaci, D. Pharmazie 1990, 45, 441-442.
- 2. Duke, S. O. Environ. Health Perspect. 1990, 87, 263-271.
- 3. Kolocouris, A.; Dimas, K.; Pannecouque, C.; Witvrouw, M.; Foscolos, G. B.; Stamatiou, G.; Fytas, G.; Zoidis, G.; Kolocouris, N.; Andrei, G. et al. Bioorg. Med. Chem. Lett. 2002, 12, 723-727.
- 4. Goda, F. E.; Abdel-Aziz, A. A.; Attef, O. A. Bioorg. Med. Chem. 2004, 12, 1845-1852.
- 5. Mohamed, S. F.; Youssef, M. M.; Amr, A. E. E.; Kotb, E. R. Sci. Pharm. 2008, 76, 279-303.
- 6. Prasad, Y. R.; Kumar, P. P.; Kumar, P. R.; Rao, A. S. E-J. Chem. 2008, 5, 144-148.
- 7. Patel, A. K.; Patel, N. H.; Patel, M. A.; Brahmbhatt, D. I. Arkivoc 2010, 11, 28-38.
- 8. Metzer, J. V. The Chemistry of Heterocyclic Compounds: Thiazole and Its Derivatives ; Wiley-VCH: New York, NY, USA, 1979.
- 9. Amnerkar, N. D.; Bhongade, B. A.; Bhusari, K. P. Arab. J. Chem. 2014, 8, 545-552.
- 10. Mahajan, N. S.; Jadhav, R. L.; Pimpodkar, N. V.; Mali, K. K.; Manikrao, A. M. Int. J. Chem. Sci. 2008, 6, 605-612.
- 11. Mahajan, N. S.; Pattan, S. R.; Jadhav, R. L.; Pimpodkar, N. V.; Manikrao, A. M. Int. J. Chem. Sci. 2008, 6, 800-806.
- 12. Saravanan, G.; Alagarsamy, V.; Pavitra, T. G. V.; Chanukya-Kumar, G.; Naresh, L.; Avinash, P. Int. J. Pharm. Bio Sci. 2010, 1, 1-8.
- 13. Singh, A. K.; Mishra, G.; Jyoti, K. J. App. Pharm. Sci. 2011, 1, 44-49.
- 14. Davood, K. M.; Gomha, S. M. J. Heterocyclic Chem. 2015, 52, 1400-1405.
- 15. Joseph, A.; Shah, C. S.; Kumar, S. S.; Alex, A. T.; Maliyakkal, N.; Moorkoth, S.; Mathew, J. E. Acta Pharm. 2013, 63, 397-408.
- 16. Bhongade, B. A.; Talath, S.; Gadad, R. A.; Gadad, A. K. J. Saudi Chem. Soc. 2016, 20, 463-475.
- 17. Davood, K. M.; Farghaly, T. A. Exp. Opi. Thera. Patents 2017, 27, 1-29.
- 18. Greider, C. W.; Blackburn, E. H. Cell 1985, 43, 405-413.
- 19. Artandi, S. E.; Depinho, R. A. Carcinogenesis 2010, 31, 9-18.
- 20. Shay, J. W.; Reddel, R. R.; Wright, W. E. Science 2012, 336, 1388-1390.
- 21. Buseman, C. M.; Wright, W. E.; Shay, J. W. Mut. Res. 2012, 730, 90-97.
- 22. Shay, J. W.; Wright, W. E. Can. Cell. 2002, 2, 257-262.
- 23. de Jesus, B. B.; Vera, E.; Schneeberger, K.; Tejera, A. M.; Ayuso, E.; Bosch, F.; Blasco, M. A. EMBO Mol. Med. 2012, 4, 691-704.
- 24. de Jesus, B. B.; Blasco, M. A. Tren. Gen. 2013, 29, 513-520.
- 25. Mitchell, M.; Futahashi, M.; Fujiwara, H.; Skordalakes, E. Nat. Struct. Mol. Bio. 2010, 17, 513-518.
- 26. Jiang, J.; Miracco, E. J.; Hong, K.; Eckert, B.; Chan, H.; Cash, D. D.; Min, B.; Zhou, Z. H.; Collins, K.; Feigon, J. Nature 2013, 496, 187-192.