[KSCI] Korea Science Citation Index Service

http://dx.doi.org/10.13160/ricns.2011.4.3.210

Holographic Quantitative Structure-Activity Relationship (HQSAR) Study of 3,4-Dihydroxychalcone Derivatives as 5-Lipoxygenase Inhibitors

Gadhe, Changdev G. (Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research)

Publication Information

Journal of Integrative Natural Science / v.4, no.3, 2011 , pp. 210-215 More about this Journal

Abstract

Holographic quantitative structure-activity relationships (HQSAR) is a useful tool to correlates structures with their biological activities. HQSAR is a two dimensional (2D) QSAR methodology, which generates QSAR equations through 2D fingerprint and correlates it with biological activity. Here, we report a 2D-QSAR model for a series of fifty-one 3,4-dihydroxychalcones derivatives utilizing HQSAR methodology. We developed HQSAR model with 6 optimum numbers of components (ONC), which resulted in cross-validated correlation coefficient ( $q^2$ ) of 0.855 with 0.283 standard error of estimate (SEE). The non-cross-validated correlation coefficient (r2) with 0.966 indicates the model is predictive enough for analysis. Developed HQSAR model was binned in to a hologram length of 257. Atomic contribution map revealed the importance of dihydroxy substitution on phenyl ring.

Keywords

HQSAR; 2D-QSAR; 5-Lipoxygenase; Fragment Fingerprint;

Citations & Related Records

Reference

1	S. E. Dahlen, P. Hedqvist, S. Hammarstrom, and B. Samuelsson, "Leukotrienes are potent constrictors of human bronchi", Nature, Vol. 288, pp.484- 486, 1980. DOI ScienceOn
2	J. M. Drazen, K. F. Austen, R. A. Lewis, D. A. Clark, G. Goto, A. Marfat, and E. J. Corey, "Comparative airway and vascular activities of leukotrienes C-1 and D in vivo and in vitro", Proc. Nat. Acad. Sci., Vol. 77, pp.4354-4358, 1980. DOI ScienceOn
3	R. D. Camp, A. A. Coutts, M. W. Greaves, A. B. Kay and M. J. Walport, "Responses of human skin to intradermal injection of leukotrienes C4, D4 and B4", Br. J. Pharmacol., Vol. 80, pp. 497-502, 1983. DOI ScienceOn
4	A. W. Ford-Hutchinson, M. A. Bray, M. V. Doig, M. E. Shipley and M. J. H. Smith, "Leukotriene B, a potent chemokinetic and aggregating substance released from polymorphonuclear leukocytes", Nature, Vol. 286, pp. 264-265, 1980. DOI ScienceOn
5	J. H. Musser and A. F. Kreft, "5-Lipoxygenase: Properties, Pharmacology, and the Quinotinyl (bridged) Aryl Class of Inhibitors", J. Med. Chem., Vol. 35, pp. 2501-2524, 1992. DOI
6	D. G. Batt, G. D. Maynard, J. J. Petraitis, J. E. Shaw, W. Galbraith and R. R. Harris, "2-Substituted-1- naphthols as Potent 5-Lipoxygenase Inhibitors with Topical Antiinflammatory Activity", J. Med. Chem., Vol. 33,pp. 360-370, 1989.
7	G. H. Jones, M. C. Venuti, J. M. Young, D. V. K. Murthy, B. E. Loe, R. A. Simpson, A. H. Berks, K. C. Kappas, C. C. Beard, S. H. Unger and P. Cheung, "Topical Nonsteroidal Antipsoriatic Agents. 1.1,2,3, 4-Tetraoxygena-N aphthalene Derivatives", J. Med. Chem. Vol. 29, pp. 1504-1511, 1986. DOI
8	H. Degreef, P. Docks, P. De Doncker, K. De Beule and G. Cauwenbergh, "A Double-Blind Vehicle- Controlled Study of R-68-131 in Psoriasis - A Topical 5-Lipoxygenase Inhibitor", J. Am. Acad. Dermatol., Vol. 22, pp. 751-755, 1990. DOI ScienceOn
9	D. G. Batt, "5-Lipoxygenase Inhibitors and Their Anti-inflammatory Activities", Progr. Med. Chem., Vol. 29, pp. 1-63, 1992.
10	P. Bruneau, C. Delvare, M. P. Edwards and R. M. McMillan, "Indazolinones, a New Series of Redox- Active 5-lipoxygenase Inhibitors with Built In Selectivity and Oral Activity", J . Med. Chem., Vol. 34, pp. 1028-1036, 1991. DOI
11	T. Nakadate, E. Aizu, S. Yamamoto and R. Kato, "Effects of Chalcone Derivatives on Lipoxygenase and Cyclooxygenase Activities of Mouse Epidermis", Prostaglandins, Vol. 30, pp. 357-367, 1985. DOI ScienceOn
12	S. Sogawa, Y. Nihro, H. Ueda, A. Izumi, T. Miki, H. Matsumoto and T. Satoh, "3, 4-Dihydroxychalcones as potent 5-lipoxygenase and cyclooxygenase inhibitors", J. Med. Chem., Vol. 36, pp. 3904-3909, 1993. DOI ScienceOn
13	S. H. R. SYBYL8.1; Tripos Inc. St. Louis, MO 63144 USA.
14	T. Hurst and T. Heritage, "HQSAR-A highly predictive QSAR technique based on molecular holograms", 213th ACS Natl. Meeting San Francisco, CA, 1997, CINF 019; 1997.
15	S. Ash, M. A. Cline, R. W. Homer, T. Hurst and G. B. Smith, "SYBYL Line Notation (SLN): A Versatile Language for Chemical Structure Representation", J. Chem. Inf. Comput. Sci., Vol. 37, pp. 71- 79, 1997. DOI ScienceOn