Franko BURČUL, Irena ŠKORIĆ, Ivana ŠAGUD

Naphthoxazoles and heterobenzoxazoles: cholinesterase inhibition and antioxidant activity

Finding novel cholinesterase inhibitors that would be able to cross the blood–brain barrier, have favorablepharmacokinetic parameters, and reduce hepatotoxicity along with other side effects has been the main focus of investigations dealing with Alzheimer disease. In this study we evaluated cholinesterase inhibitory and antioxidant activity ofseven oxazole derivatives. These compounds have been efficiently and sustainably prepared by photochemical electrocyclization reaction. Various naphthoxazoles have been previously investigated as potential antibacterial, antituberculosis,and anticancer agents. They have also been tested for antioxidant activity, but never for cholinesterase inhibitoryactivity. Among the tested oxazole derivatives, fused heterobenzoxazole compounds with pyridine and thiophene moiety, oxazolo[5,4-h]isoquinoline, thieno[2’,3’:5,6]benzo[1,2-d]oxazole, and thieno[3’,2’:5,6]benzo[1,2-d]oxazole, showed thegreatest potential for both cholinesterase inhibitory and antioxidant activity. Among them, thieno[2’,3’:5,6]benzo[1,2-d]oxazole was found to be the best one.

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1. Bayani, U.; Ajay, V. S.; Paolo, Z.; Mahajan, R. T. Curr. Neuropharmacol. 2009, 7, 65-74.
2. Gülçin, I.; Kireçci, E.; Akkemik, E.; Fevzi, T.; Hisar, O. Turk. J. Biol. 2010, 34, 175-188.
3. Öztaskın, N.; Taslimi, P.; Maraş, A.; Gülcin, İ.; Göksu, S. Bioorg. Chem. 2017, 74, 104-114.
4. Kukull, W. A.; Higdon, R.; Bowen, J. D. Arch. Neurol. 2002, 59, 1737-1746.
5. Tarawneh, R.; Holtzman, D. M. Cold. Spring. Harb. Perspect. Med. 2012, 2, 1-17.
6. Burčul, F.; Radan, M.; Politeo, O.; Blažević, I. In Advances in Chemistry Research; Taylor, J. C., Ed. Nova Science Publishers: New York, NY, USA, 2017, pp. 1-71.
7. Gulçin, İ.; Abbasova, M.; Taslimi, P.; Huyut, Z.; Safarova, L.; Sujayev, A.; Farzaliyev, V.; Beydemir, Ş.; Alwasel, S. H.; Supuran, C. T. J. Enzyme Inhib. Med. Chem. 2017, 32, 1174-1182.
8. Akıncıoğlu, A.; Kocaman, E.; Akıncıoğlu, H.; Salmas, R.E.; Durdagi, S.; Gülçin, İ.; Supuran, C. T.; Göksu, S. Bioorg. Chem. 2017, 74, 238-250.
9. Fisher, N. I.; Hamer, F. M. J. Chem. Soc. (Resumed) 1934, 962-965.
10. Desai, R. D.; Hunter, R. F.; Khalidi, A. R. K. J. Chem. Soc. (Resumed) 1938, 321-329.
11. Hall, J. H.; Chien, J. Y.; Kauffman, J. M.; Litak, P. T.; Adams, J. K.; Henry, R. A.; Hollins, R. A. J. Heterocycl. Chem. 1992, 29, 1245-1273.
12. Katritzky, A. R.; Rachwal, B.; Rachwal, S.; Macomber, D.; Smith, T. P. J. Heterocycl. Chem. 1993, 30, 135-139.
13. Moskal, J.; Van Stralen, P.; Postma, D.; Van Leusen, A.M. Tetrahedron Lett. 1986, 27, 2173-2176.
14. Nicolaides, D. N.; Awad, R. W.; Papageorgiou, G. K.; Kojanni, E.; Tsoleridis, C. A. J. Heterocycl. Chem. 1997, 34, 1651-1656.
15. Nicolaides, D. N.; Awad, R. W.; Varella, E. A. J. Heterocycl. Chem. 1996, 33, 633-637.
16. Novikov, R. A.; Klimenko, I. P.; Shulishov, E. V.; Korolev, V. A.; Tomilov, Y. V. Russ. Chem. Bull. 2008, 57, 1718-1724.
17. Somayajulu, V. V.; Subba Rao, N. V. Proc. Indian Acad. Sci.-Section A 1965, 61, 139-145.
18. Ashton, W. T.; Sisco, R. M.; Dong, H.; Lyons, K. A.; He, H.; Doss, G. A.; Leiting, B.; Patel, R. A.; Wu, J. K.; Marsilio, F. et al. Bioorg. Med. Chem. Lett. 2005, 15, 2253-2258.
19. Kumar, A.; Ahmad, P.; Maurya, R. A.; Singh, A. B.; Srivastava, A. K. Eur. J. Med. Chem. 2009, 44, 109-116.
20. Ryu, C. K.; Lee, R. Y.; Kim, N. Y.; Kim, Y. H.; Song, A. L. Bioorg. Med. Chem. Lett. 2009, 19, 5924-5926.
21. Sobarzo-Sánchez, E.; Jullian, C.; Cassels, B. K.; Saitz, C. Synth. Commun. 2002, 32, 3687-3693.
22. Voets, M.; Antes, I.; Scherer, C.; Müller-Vieira, U.; Biemel, K.; Barassin, C.; Marchais-Oberwinkler, S.; Hartmann, R. W. J. Med. Chem. 2005, 48, 6632-6642.
23. Voight, E. A.; Daanen, J. F.; Kort, M. E. J. Org. Chem. 2010, 75, 8713-8715.
24. Yeh, V. S. C. Tetrahedron 2004, 60, 11995-12042.
25. Eswaran, S.; Adhikari, A. V.; Ajay Kumar, R. Eur. J. Med. Chem. 2010, 45, 957-966.
26. Moura, K. C. G.; Carneiro, P. F.; Pinto, M. D. C. F. R.; da Silva, J. A.; Malta, V. R. S.; de Simone, C. A.; Dias, G. G.; Jardim, G. A. M.; Cantos, J.; Coelho, T. S. et al. Bioorg. Med. Chem. 2012, 20, 6482-6488.
27. Kumar, D.; Jacob, M. R.; Reynolds, M. B.; Kerwin, S. M. Bioorg. Med. Chem. 2002, 10, 3997-4004.
28. Wang, X. Z.; Yao, J. H.; Xie, Y. Y.; Lin, G. J.; Huang, H. L.; Liu, Y. J. Inorg. Chem. Commun. 2013, 32, 82-88.
29. Šagud, I.; Faraguna, F.; Marinić, Ž.; Šindler-Kulyk, M. J. Org. Chem. 2011, 76, 2904-2908.
30. Prior, R. L.; Wu, X.; Schaich, K. J. Agric. Food Chem. 2005, 53, 4290-4302.
31. Sussman, J.; Harel, M.; Frolow, F.; Oefner, C.; Goldman, A.; Toker, L.; Silman, I. Science 1991, 253, 872-879.
32. Nachon, F.; Masson, P.; Nicolet, Y.; Lockridge, O.; Fontecilla-Camps, J. C. In Butyrylcholinesterase: Its Function and Inhibitors; Giacobini, E., Ed. Martin Dunitz Ltd.: London, UK, 2003, pp. 39-54.
33. Burčul, F.; Generalić Mekinić, I.; Radan, M.; Rollin, P.; Blažević, I. J. Enzyme Inhib. Med. Chem. 2018, 33, 577-582.
34. Benzie, I. F. F.; Strain, J. J. Anal. Biochem. 1996, 239, 70-76.