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Combined 3D-QSAR modeling and molecular docking study on quinoline derivatives as inhibitors of P-selectin.
Chem Biol Drug Des. 2009 Dec; 74(6):596-610.CB

Abstract

P-selectin is a promising target for developing novel atherosclerosis drugs. To understand the structure-activity correlation of quinolines-based P-selectin inhibitors, we have carried out a combined molecular docking and three-dimensional quantitative structure-activity relationship (3D-QSAR) modeling study. The study has resulted in two types of satisfactory 3D-QSAR models, including the CoMFA model (r(2), 0.863; q(2), 0.589) and CoMSIA model (r(2), 0.866; q(2), 0.636), to predict the biological activity of new compounds. The detailed microscopic structures of P-selectin binding with inhibitors have been studied by molecular docking. We have also developed docking based 3D-QSAR models (CoMFA with r(2), 0.934; q(2), 0.591; CoMSIA with r(2), 0.896; q(2), 0.573). The contour maps obtained from the 3D-QSAR models in combination with the docked binding structures help to better interpret the structure-activity relationship. All of the structural insights obtained from both the 3D-QSAR contour maps and molecular docking are consistent with the available experimental activity data. The satisfactory results strongly suggest that the developed 3D-QSAR models and the obtained P-selectin-inhibitor binding structures are reasonable for the prediction of the activity of new inhibitors and in future drug design.

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Authors+Show Affiliations

Zeng H
Key Laboratory of Radiopharmaceuticals of Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China. hbzhang@bnu.edu.cn
Cao R
No affiliation info available
Zhang H
No affiliation info available

MeSH

AtherosclerosisBinding SitesComputer SimulationHumansModels, ChemicalP-SelectinQuantitative Structure-Activity RelationshipQuinolinesSoftware

Pub Type(s)

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

Language

eng

PubMed ID

19843078

Citation

Zeng, Huahui, et al. "Combined 3D-QSAR Modeling and Molecular Docking Study On Quinoline Derivatives as Inhibitors of P-selectin." Chemical Biology & Drug Design, vol. 74, no. 6, 2009, pp. 596-610.
Zeng H, Cao R, Zhang H. Combined 3D-QSAR modeling and molecular docking study on quinoline derivatives as inhibitors of P-selectin. Chem Biol Drug Des. 2009;74(6):596-610.
Zeng, H., Cao, R., & Zhang, H. (2009). Combined 3D-QSAR modeling and molecular docking study on quinoline derivatives as inhibitors of P-selectin. Chemical Biology & Drug Design, 74(6), 596-610. https://doi.org/10.1111/j.1747-0285.2009.00893.x
Zeng H, Cao R, Zhang H. Combined 3D-QSAR Modeling and Molecular Docking Study On Quinoline Derivatives as Inhibitors of P-selectin. Chem Biol Drug Des. 2009;74(6):596-610. PubMed PMID: 19843078.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Combined 3D-QSAR modeling and molecular docking study on quinoline derivatives as inhibitors of P-selectin. AU - Zeng,Huahui, AU - Cao,Ran, AU - Zhang,Huabei, Y1 - 2009/10/20/ PY - 2009/10/22/entrez PY - 2009/10/22/pubmed PY - 2010/1/23/medline SP - 596 EP - 610 JF - Chemical biology & drug design JO - Chem Biol Drug Des VL - 74 IS - 6 N2 - P-selectin is a promising target for developing novel atherosclerosis drugs. To understand the structure-activity correlation of quinolines-based P-selectin inhibitors, we have carried out a combined molecular docking and three-dimensional quantitative structure-activity relationship (3D-QSAR) modeling study. The study has resulted in two types of satisfactory 3D-QSAR models, including the CoMFA model (r(2), 0.863; q(2), 0.589) and CoMSIA model (r(2), 0.866; q(2), 0.636), to predict the biological activity of new compounds. The detailed microscopic structures of P-selectin binding with inhibitors have been studied by molecular docking. We have also developed docking based 3D-QSAR models (CoMFA with r(2), 0.934; q(2), 0.591; CoMSIA with r(2), 0.896; q(2), 0.573). The contour maps obtained from the 3D-QSAR models in combination with the docked binding structures help to better interpret the structure-activity relationship. All of the structural insights obtained from both the 3D-QSAR contour maps and molecular docking are consistent with the available experimental activity data. The satisfactory results strongly suggest that the developed 3D-QSAR models and the obtained P-selectin-inhibitor binding structures are reasonable for the prediction of the activity of new inhibitors and in future drug design. SN - 1747-0285 UR - https://www.unboundmedicine.com/medline/citation/19843078/Combined_3D_QSAR_modeling_and_molecular_docking_study_on_quinoline_derivatives_as_inhibitors_of_P_selectin_ L2 - https://doi.org/10.1111/j.1747-0285.2009.00893.x DB - PRIME DP - Unbound Medicine ER -