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3D-QSAR Analysis of Antidepressant, Tricyclic Isoxazole Analogues against para-Chloroamphetamine-induced Excitation  

Choi, Min-Sung (Sky Solution Inc., Business Incubation Center, Chungnam National University)
Sung, Nack-Do (Sky Solution Inc., Business Incubation Center, Chungnam National University)
Myung, Pyung-Keun (College of Pharmacy, Chungnam National University)
Publication Information
YAKHAK HOEJI / v.55, no.2, 2011 , pp. 91-97 More about this Journal
Abstract
To search a new anti-depressant agents against para-chloroamphetamine-induced excitation, three dimensional quantitative-structure relationships (3D-QSAR) models between structure of 3a,4-dihydro-3H-[1]-benzopyronao[4,3]isoxazoles (1-30) and thieir inhibitory activity against para-chloroamphetamine-induced excitation were performed and discussed quantitatively using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods. From these basis on the findings, the optimized CoMSIA-2F model ($q^2$=0.793 and $r^2$=0.952) showed the best statistical results. And also, it is found that the para-chloroamphetamine inhibitory activity from the optimized CoMSIA-2F model was dependent on steric field (35.2%) and electrostatic field (64.8%) of tricyclic isoxazoles. Particularly, it is predicted that the inhibitory activity against para-chloroamphetamine-induced excitation will be able to increase by the designed compounds from the CoMSIA-2F model.
Keywords
para-chloroamphetamine-induced excitation; tricyclic isoxazoles; new anti-depressant agents; 3D-QSAR;
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1 Beyer, C. E., Lin, Q., Rosenzweig-Lipson, S. and Schechter, L. E. : Alpha 2A-adrenoceptors enhance the serotonergic effects of fluoxetine. Eur. J. Pharmacol. 539, 164 (2006).   DOI   ScienceOn
2 Blier, P. : Pharmacology of rapid-onset antidepressant treatment strategies. J. Clin. Psychiatry 62 Suppl 15, 12 (2001).   DOI
3 Pastor, J., Alcazar, J., Alvarez, R. M., Andres, J. I. Cid, J. M., De Lucas, A. I., Diaz, A., Fernandez, J., Font, L. M., Iturrino, L., Lafuente, C., Martinez, S., Bakker, M. H., Biesmans, I., Heylen, L. I. and Megens, A. A. : Synthesis of 3a,4-dihydro-3H-[1]benzopyrano[4,3-c]isoxazoles, displaying combined 5-HT uptake inhibiting and alpha2-adrenoceptor antagonistic activities. Part 2: Further exploration on the cinnamyl moiety. Bioorg. Med. Chem. Lett. 14, 2917 (2004).   DOI   ScienceOn
4 Clark, M. and Cramer, R. : Comparative molecular field analysis (CoMFA). 2. Toward its use with 3D-structural databases. Tetrahedron Computer Methodology 3, 47 (1990).   DOI
5 Tripos, S. : Molecular modeling and QSAR software on CDRom (Ver. 7.3), Tripos Associates, Inc., 1699 S. Hanley Road, Suite 303, 63144 (2001).
6 Vasan, A. and Raju, K. : Comparative analysis of Simulated Annealing, Simulated Quenching and Genetic Algorithms for optimal reservoir operation. Applied. Soft. Computing 9, 274 (2009).   DOI   ScienceOn
7 Soung, M., Lee, Y. and Sung, N. : 3D-QSARs of Herbicidal 2-N-Phenylisoindolin-1-one Analogues as a New Class of Potent Inhibitors of Protox. Bull. Kor. Che. Soc. 30, 613 (2009).   DOI
8 Marshall, G., Barry, C., Bosshard, H., Dammkoehler, R. and Dunn, D. : The conformational parameter in drug design: the active analog approach. In Computer-assisted Drug Design 112, 205 (1979).
9 Cramer III, R., Bunce, J., Patterson, D. and Frank, I. : Crossvalidation, bootstrapping, and partial least squares compared with multiple regression in conventional QSAR studies. Quant. Struct.-Act. Relat. 7, 18 (1988).   DOI
10 Lindberg, W., Persson, J. and Wold, S. : Partial least-squares method for spectrofluorimetric analysis of mixtures of humic acid and lignin sulfonate. Analytical Chemistry 55, 643 (1983).   DOI
11 Rang, H., Dale, M., Ritter, J. and Moore, P. : Pharmacology. 5th Edition. Edinburgh, Churchill Livingstone. for Noradrenalin system, p. 186 (2003).
12 Krogsgaard-Larsen, P., Liljefors, T. and Madsen, U. : Textbook of drug design and discovery. Taylor & Francis, London (2002).
13 Gumnick, J. F. and Nemeroff, C. B. : Problems with currently available antidepressants. J. Clin. Psychiatry 61 Suppl 10, 5 (2000).
14 Maze, M. and Tranquilli, W. : Alpha-2 adrenoceptor agonists: defining the role in clinical anesthesia. Anesthesiology 74, 581 (1991).   DOI   ScienceOn
15 Sherman, A., Gal, E. M., Fuller, R. W. and Molloy, B. B. : Effects of intraventricular p-chloroamphetamine and its analogues on cerebral 5-HT. Neuropharmacology 14, 733 (1975).   DOI   ScienceOn
16 Andres, J. I., Alcazar, J., Alonso, J. M., Alvarez, R. M., Bakker, M. H., Biesmans, I., Cid, J. M., De Lucas, A. I., Fernandez, J., Font, L. M., Hens, K. A., Iturrino, L., Lenaerts, I., Martinez, S., Megens, A. A., Pastor, J., Vermote, P. C. and Steckler, T. : Discovery of a new series of centrally active tricyclic isoxazoles combining serotonin (5-HT) reuptake inhibition with alpha2-adrenoceptor blocking activity. J. Med. Chem. 48, 2054 (2005).   DOI   ScienceOn
17 Andres, J. I., Alcazar, J., Alonso, J. M., Alvarez, R. M., Cid, J. M., De Lucas, A. I., Fernandez, J., Martinez, S., Nieto, C., Pastor, J., Bakker, M. H., Biesmans, I., Heylen, L. I. and Megens, A. A. : Synthesis of 3a,4-dihydro-3H-[1]benzopyrano [4,3-c]isoxazoles, displaying combined 5-HT uptake inhibiting and alpha(2)-adrenoceptor antagonistic activities: a novel series of potential antidepressants. Bioorg. Med. Chem. Lett. 13, 2719 (2003).   DOI   ScienceOn
18 Andres, J. I., Alcazar, J., Alonso, J. M., De Lucas, A. I., Iturrino, L., Biesmans, I. and Megens, A. A. : Synthesis of 7-amino-3a,4-dihydro-3H-[1]benzopyrano[4,3-c]isoxazole derivatives displaying combined alpha2-adrenoceptor antagonistic and 5-HT reuptake inhibiting activities. Bioorg. Med. Chem. 14, 4361 (2006).   DOI   ScienceOn
19 Murthy, R., Bertolote, J., Epping-Jordan, J., Funk, M., Prentice, T., Saraceno, B. and Saxena, S. : The World Health report: 2001: Mental health: new understanding, new hope. World Health Organization, Geneva, Switzerland (2001).
20 Murray, C. J. and Lopez, A. D. : Alternative projections of mortality and disability by cause 1990-2020: Global burden of disease study. Lancet 349, 1498 (1997).   DOI   ScienceOn
21 이충경, 박강규, 조맹제, 정은기, 김장규, 김선욱 : 2006 정신질환실태 역학조사. 서울: 보건복지부 (2008).
22 Sanders, A., Detera-Wadleigh, S. and Gershon, E. : Molecular genetics of mood disorders. Neurobiology of Mental Illness. New York, Oxford, 299 (1999).
23 Akiskal, H. : Mood disorders: introduction and overview. Comprehensive Textbook of Psychiatry. 7th ed. Baltimore, MD: Lippincott Williams and Wilkins, 1284 (2000).
24 Fava, M. and Kendler, K. S. : Major depressive disorder. Neuron 28, 335 (2000).   DOI   ScienceOn
25 Hindmarch, I. : Expanding the horizons of depression: beyond the monoamine hypothesis. Hum. Psychopharmacol. 16, 203 (2001).   DOI   ScienceOn
26 Guze, S. and Robins, E. : Suicide and primary affective disorders. Br. J. Psychiatry 117, 437 (1970).   DOI   ScienceOn
27 Edwards, J. : Selective serotonin reuptake inhibitors. Br. Med. J. 304, 1644 (1992).   DOI   ScienceOn
28 The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR). American Psychiatric Association, Washington, DC (2000).