Tuğba TAŞKIN TOK, Özgün ÖZAŞIK, Deniz SARIGÖL, Ayşe UZGÖREN BARAN

Synthesis and molecular modeling studies of naproxen-based acyl hydrazone derivatives

A series of N-acylhydrazone derivatives (2a--2p) containing 6-methoxy-naphthalene and acylhydrazone moieties were synthesized in good yield using microwave irradiation and developed as potential COX-2 inhibitors. Furthermore, the interactions between COX-2 and the compounds were examined in detail by molecular modeling studies such as structure--activity relationship and molecular docking performed using Gaussian 09 and Discovery Studio 3.5. As a result, it was found that N-acylhydrazone compounds displayed a different mechanism than SC-558 as COX-2 inhibitor by binding to different active sites of the protein, COX-2. Compound 2c would be a good COX-2 inhibitor candidate for preclinical studies.

Anahtar Kelimeler:

Naproxen, microwave, acyl hydrazones, molecular docking

Synthesis and molecular modeling studies of naproxen-based acyl hydrazone derivatives

Keywords:

Naproxen, microwave, acyl hydrazones, molecular docking,

PDF

___

Vane, J. R. Nature-New Biol. 1971, 231, 232–235.
Unsal-Tan, O.; Ozden, K.; Rauk, A.; Balkan, A. Eur J. Med. Chem. 2010, 45, 2345–2352.
Pratico, D.; Dogne, J. M. Circulation 2005, 112, 1073–1079.
Watson, D. J.; Rhodes, T.; Cai, B.; Guess, H. A. Arch. Intern. Med. 2002, 162, 1105–1110.
Farkouh, M. E.; Greenberg, J. D.; Jeger, R. V.; Ramanathan, K.; Verheugt, F. W. A.; Chesebro, J. H.; Kirshner,
H.; Hochman, J. S.; Lay, C. L.; Ruland, S.; et al. Ann. Rheum. Dis. 2007, 66, 764–770.
Biskupiak, J. E.; Brixner, D. I.; Howard, K.; Oderda, G. M. J. Pain Pall. Care Pharmacother. 2006, 20, 7–14.
Chan, F. K. Nat. Clin. Pract. Gastroenterol. Hepatol. 2006, 3, 563–573.
Garcia Rodriguez, L. A.; Jick, H. Lancet 1994, 343, 769–772.
Leach, A. Molecular Modelling: Principles and Applications; Prentice Hall: Upper Saddle River, NJ, USA, 2001.
Friedman, R. Biochem. J. 2011, 438, 415–426.
Uzgoren-Baran, A.; Tel, B. C.; Sarigol, D.; Ozturk, E. I., Kazkayasi, I.; Okay, G.; Ertan, M.; Tozkoparan, B. Eur J. Med. Chem. 2012, 57, 398–406.
Nakka, M.; Begum, M. S.; Varaprasad, B. F. M.; Reddy, L. V.; Bhattacharya, A.; Helliwell, M.; Mukherjee, A. K.; Beevi, S. S.; Mangamoori, L. N.; Mukkanti, K.; et al. J . Chem. Pharm. Res. 2010, 2, 393–409.
Palla, G.; Predieri, G.; Domiano, P.; Vignali, C.; Turner, W. Tetrahedron 1986, 42, 3649–3654.
Podyachev, S. N.; Litvinov, I. A.; Shagidullin, R. R.; Buzykin, B. I.; Bauer, I.; Osyanina, D. V.; Awakumova, L. V.; Sudakova, S. N.; Habicher, W. D.; Konovalov, A. I.; et al. Spectrochim. Acta A 2007, 66, 250–261.
Gaussian 09, Revision A.1, Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; et al. Gaussian, Inc., Wallingford, CT, USA, 2009.
Accelrys Software Inc., Discovery Studio 3.5, San Diego, CA, USA, 2013.
Brooks, B. R.; Bruccoleri, R. E.; Olafson, B. D.; States, D. J.; Swaminathan, S.; Karplus, M. J. Comput. Chem. 1983, 4, 187–217.
Parr, R. G.; Szentpaly, L. V.; Liu, S. J. Am. Chem. Soc. 1999, 121, 1922.
Maynard, A. T.; Huang, M.; Rice, W. G.; Covell, D. G. Proc. Natl. Acad. Sci. USA 95, 1998, 11578–11583.
Chattaraj, P. K.; Giri, S.; Duley, S. Chem. Rev. 2011, 111, 43–75.
Taskin T.; Sevin, F. J. Mol. Struct 2007, 803, 61–66.
Karelson, M.; Lobanov, V. S.; Katritzky, A. R. Chem. Rev. 1996, 96, 1027–1043.
Parthasarathi, R.; Subramanian, V.; Royb, D. R.; and Chattaraj, P. K. Bioorg. Med. Chem. 2004, 12, 5533–5543.
Ta¸skın, T., Sevin, F. Turk. J. Chem. 2011, 35, 481–498.
Kurumbail, R. G.; Stevens, A.M.; Gierse, J. K.; McDonald, J. J.; Stegeman, R. A.; Pak, J. Y.; Gildehaus, D.; Miyashiro, J. M.; Penning, T. D.; Seibert, K.; et al. Nature 1996, 384, 644–648.