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Docking-based 3D-QSAR study for 11beta-HSD1 inhibitors.
Bioorg Med Chem Lett. 2008 Apr 01; 18(7):2479-90.BM

Abstract

11beta-Hydroxysteroid dehydrogenase (11beta-HSD) enzymes catalyze the conversion of biologically inactive 11-ketosteroids into their active 11beta-hydroxy derivatives and vice versa. 11beta-HSD1 has been studied as a potential treatment for metabolic disease such as diabetes and obesity. To find correlation between 11beta-HSD1 and inhibitors, three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were performed on 70 inhibitors, based on molecular docking conformations obtained by using FlexX-Pharm. The studies include comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Based on the docking results, highly predictive 3D-QSAR models were developed with q(2) values of 0.543 and 0.519 for CoMFA and CoMSIA, respectively. A comparison of the 3D-QSAR field contributions with the structural features of the binding site showed good correlation between the two analyses. Therefore, these results should be useful to the prediction of the activities of new 11beta-HSD1 inhibitors.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Lee JH
Center for Drug Discovery Technologies, Korea Research Institute of Chemical Technology, Yu seong-gu, Daejon 305-600, Republic of Korea.
Kang NS
No affiliation info available
Yoo SE
No affiliation info available

MeSH

11-beta-Hydroxysteroid Dehydrogenase Type 1AlgorithmsBinding SitesComputer SimulationEnzyme InhibitorsLigandsMolecular ConformationQuantitative Structure-Activity RelationshipSubstrate Specificity

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18314331

Citation

Lee, Jin Hee, et al. "Docking-based 3D-QSAR Study for 11beta-HSD1 Inhibitors." Bioorganic & Medicinal Chemistry Letters, vol. 18, no. 7, 2008, pp. 2479-90.
Lee JH, Kang NS, Yoo SE. Docking-based 3D-QSAR study for 11beta-HSD1 inhibitors. Bioorg Med Chem Lett. 2008;18(7):2479-90.
Lee, J. H., Kang, N. S., & Yoo, S. E. (2008). Docking-based 3D-QSAR study for 11beta-HSD1 inhibitors. Bioorganic & Medicinal Chemistry Letters, 18(7), 2479-90. https://doi.org/10.1016/j.bmcl.2008.02.042
Lee JH, Kang NS, Yoo SE. Docking-based 3D-QSAR Study for 11beta-HSD1 Inhibitors. Bioorg Med Chem Lett. 2008 Apr 1;18(7):2479-90. PubMed PMID: 18314331.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Docking-based 3D-QSAR study for 11beta-HSD1 inhibitors. AU - Lee,Jin Hee, AU - Kang,Nam Sook, AU - Yoo,Sung-Eun, Y1 - 2008/02/19/ PY - 2007/11/27/received PY - 2008/01/21/revised PY - 2008/02/14/accepted PY - 2008/3/4/pubmed PY - 2008/7/9/medline PY - 2008/3/4/entrez SP - 2479 EP - 90 JF - Bioorganic & medicinal chemistry letters JO - Bioorg Med Chem Lett VL - 18 IS - 7 N2 - 11beta-Hydroxysteroid dehydrogenase (11beta-HSD) enzymes catalyze the conversion of biologically inactive 11-ketosteroids into their active 11beta-hydroxy derivatives and vice versa. 11beta-HSD1 has been studied as a potential treatment for metabolic disease such as diabetes and obesity. To find correlation between 11beta-HSD1 and inhibitors, three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were performed on 70 inhibitors, based on molecular docking conformations obtained by using FlexX-Pharm. The studies include comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Based on the docking results, highly predictive 3D-QSAR models were developed with q(2) values of 0.543 and 0.519 for CoMFA and CoMSIA, respectively. A comparison of the 3D-QSAR field contributions with the structural features of the binding site showed good correlation between the two analyses. Therefore, these results should be useful to the prediction of the activities of new 11beta-HSD1 inhibitors. SN - 1464-3405 UR - https://www.unboundmedicine.com/medline/citation/18314331/Docking_based_3D_QSAR_study_for_11beta_HSD1_inhibitors_ DB - PRIME DP - Unbound Medicine ER -