Tuğba TAŞKIN, Fatma SEVİN

QSAR and docking studies of inhibition activity of 5,6-dihydro 11-alkylbenzo[a]carbazole derivatives against estrogen receptor

In the present study, QSAR and docking studies were applied to understand the nature of 5,6-dihydro 11-alkylbenzo[a]carbazole derivatives and to investigate the interactions of homolog series with binding sites on selected a-chains of human estrogen receptors (hER). The best QSAR model was selected, having the correlation coefficient r = 0.924, squared correlation coefficient r2 = 0.854, standard deviation s = 0.357, and cross-validated squared correlation coefficient Q2 = 0.755. The QSAR model indicated that the descriptors E-HOMO and heat of formation play an important role in human estrogen receptor inhibitor activities. A docking study was also utilized to visualize the interactions between the selected 2 compounds, 2 and 3, as estrogen inhibitors and human estrogen receptor. The results of the present study may be useful in the designing of more potent 5,6-dihydro 11-alkylbenzo[a]carbazole derivatives as estrogen receptor inhibitor agents.

Anahtar Kelimeler:

QSAR, docking, estrogen receptor inhibitors, 5, 6-dihydro 11-alkylbenzo[a]carbazole derivatives

QSAR and docking studies of inhibition activity of 5,6-dihydro 11-alkylbenzo[a]carbazole derivatives against estrogen receptor

Keywords:

QSAR, docking, estrogen receptor inhibitors, 5, 6-dihydro 11-alkylbenzo[a]carbazole derivatives,

PDF

___

von Angerer, E.; Prekajac, J.; Strohmeier, J. J. Med. Chem. 1984, 27, 1439-1447. von Angerer, E.; Prekajac, J. J. Med. Chem. 1986, 29, 380-386.
Katritzky, W. J. Heterocyc. Chem. 1988, 25, 671-675.
Pappa, H.; Segall, A.; Pizzorno, M. T.; Radice, M.; Amoroso, A.; Gutkind, G. Il Farmaco 1994, 49, 333-336.
Segall, A.; Pappa, H.; Casaubon, R.; Martin, G.; Bergoc, R.; Pizzorno, M. T. Eur. J. Med. Chem. 1995, 30, 169.
Macchia, M.; Manera, C.; Nencetti, S.; Rossello, A.; Brocalli, G.; Limonta, D. Il Farmaco 1996, 51, 75-78.
Segall, A.; Pappa, H.; Pizzorno, M. T.; Radice, M.; Amoroso, A.; Gutkind, G. Il Farmaco 1996, 51, 513-516.
Amoroso, A.; Radice, M.; Segall, A.; Rodero, L.; Hochenfellner, F.; Pizzorno, M. T.; Moretton, J.; Garrido, D.; Gutkind, G. Pharmazie 2000, 55, 151-152.
Segall, A.; Pizzorno, M. T. Pharmazie 2000, 55, 766- 767.
Martin, G.; Cocca, C.; Rivera, E.; Cricco, G.; Segall, A.; Pappa, H.; Casaubon, R.; Caro, R.; Pizzorno, M. T.; Bergoc, R. J. Exp. Ther. Oncol. 2002, 2, 77-84.
LePecq, J. B.; Dat-Xoung, N.; Gosse, C.; Paoletti, C. Proc. Natl. Acad. Sci. 1974, 71, 5078.
Pelaprat, D.; Oberlin, R.; Le Guen, I.; Roques, B. P.; LePecq, J. B. J. Med. Chem. 1980, 23, 1330.
(a) Martin, G.; Cocca, C.; Rivera, E.; Cricco, G.; Caro, R.; Segall, A.; Pappa, H.; Casaubon, R.; Pizzorno, M. T.; Bergoc, R. M. J. Exp.Ther. Oncol. 2002, 2, 77-84. (b) Dantas, S. O.; Lavarda, F. C.; Galvao, D. S.; Laks, B. J.
Mol. Struc. Theochem. 1992, 253, 319. (c) Dantas, S. O.; Galvao, D. S. J. Mol. Struc. Theochem. 1992, 43, 257.
Poliakoﬀ, N.; Albonico, S. M.; Alvarez, M.; Pecca, J. G.; Vernengo, M. J. J. Med. Chem. 1973, 16, 1411.
Pahsa, F. A.; Srivastava, H. K.; Singh, P. P. Int. J. Quantum Chem. 2005, 104, 87-100.
Taskin, T.; Sevin, F. J. Mol. Struct.: THEOCHEM 2007, 803, 61-66.
Angerer, E.; Prekajac, J. J. Med. Chem. 1986, 3, 29.
BILIN, Donnersbergstrasse 9, D–67256 Weisenheim am Sand, Germany, 2005.
Dewar, M. J. S.; Zoebisch, E. G.; Healy, E. F.; Stewart, J. J. P. J. Am. Chem. Soc. 1985, 107, 3902.
Stewart, J. J. P. J. Comp. Chem. 1989, 10, 209.
(a) Parr, R. G.; Yang, W. Density Functional Theory of Atoms and Molecules, Oxford University Press, New York, (b) Kohn, W.; Becke, A. D.; Parr, R. G. J. Phys. Chem. 1996, 100, 12974.
Demo ICM-Pro version 3.4.8, Molsoft LLC, 3366 North Torrey Pines Court, Suite 300, La Jolla, CA 92037, USA.
Chattaraj, P. K.; Nath, S.; Maiti, B. Reactivity Descriptors. In: Tollenaere, J.; Bultinck, P.; Winter H.D.; Lange- naeker, W., Editors; Computational Medicinal Chemistry and Drug Discovery, Marcel Dekker, New York, 2003, pp. 295-322, Chapter 11.
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
Srikanth, K.; Debnath, B.; Jha, T. Bioorg. Med. Chem. 2002, 10, 1841-1854.