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3D-QSAR studies of Checkpoint Kinase Weel inhibitors based on molecular docking, CoMFA and CoMSIA.
Eur J Med Chem. 2008 May; 43(5):925-38.EJ

Abstract

Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were performed on 97 4-phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione inhibitors, based on molecular docking scores obtained by using GOLD 3.1, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices (CoMSIA). The docking results provided a reliable conformational alignment scheme for the 3D-QSAR model. Based on the docking conformations and alignments, highly predictive CoMFA and CoMSIA were obtained with cross-validated q(2) value of 0.828 and 0.796, respectively, and non-cross-validated partial least-squares (PLS) analysis with the optimum components of five showed a conventional r(2) of 0.962 and 0.949, respectively. The predictive ability was validated by compounds that were not included in the training set. Furthermore, the CoMFA and CoMSIA model plots were mapped back to the binding sites of Checkpoint Kinase Weel, to get a better understanding of vital interactions between the inhibitors and Weel kinase. As a result, we have identified some key features in the 4-phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-diones responsible for the Weel inhibitory activity that may be used to design more potent 4-phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-diones and predict their activity prior to synthesis.

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Authors+Show Affiliations

Yi P
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204, China.
Fang X
No affiliation info available
Qiu M
No affiliation info available

MeSH

Binding SitesCarbazolesHydrogen BondingModels, MolecularMolecular ConformationProtein BindingProtein-Tyrosine KinasesPyrrolesQuantitative Structure-Activity RelationshipStatic Electricity

Pub Type(s)

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

Language

eng

PubMed ID

17698256

Citation

Yi, Ping, et al. "3D-QSAR Studies of Checkpoint Kinase Weel Inhibitors Based On Molecular Docking, CoMFA and CoMSIA." European Journal of Medicinal Chemistry, vol. 43, no. 5, 2008, pp. 925-38.
Yi P, Fang X, Qiu M. 3D-QSAR studies of Checkpoint Kinase Weel inhibitors based on molecular docking, CoMFA and CoMSIA. Eur J Med Chem. 2008;43(5):925-38.
Yi, P., Fang, X., & Qiu, M. (2008). 3D-QSAR studies of Checkpoint Kinase Weel inhibitors based on molecular docking, CoMFA and CoMSIA. European Journal of Medicinal Chemistry, 43(5), 925-38.
Yi P, Fang X, Qiu M. 3D-QSAR Studies of Checkpoint Kinase Weel Inhibitors Based On Molecular Docking, CoMFA and CoMSIA. Eur J Med Chem. 2008;43(5):925-38. PubMed PMID: 17698256.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 3D-QSAR studies of Checkpoint Kinase Weel inhibitors based on molecular docking, CoMFA and CoMSIA. AU - Yi,Ping, AU - Fang,Xin, AU - Qiu,Minghua, Y1 - 2007/08/14/ PY - 2007/02/06/received PY - 2007/06/18/revised PY - 2007/06/21/accepted PY - 2007/8/19/pubmed PY - 2008/7/22/medline PY - 2007/8/19/entrez SP - 925 EP - 38 JF - European journal of medicinal chemistry JO - Eur J Med Chem VL - 43 IS - 5 N2 - Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were performed on 97 4-phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione inhibitors, based on molecular docking scores obtained by using GOLD 3.1, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices (CoMSIA). The docking results provided a reliable conformational alignment scheme for the 3D-QSAR model. Based on the docking conformations and alignments, highly predictive CoMFA and CoMSIA were obtained with cross-validated q(2) value of 0.828 and 0.796, respectively, and non-cross-validated partial least-squares (PLS) analysis with the optimum components of five showed a conventional r(2) of 0.962 and 0.949, respectively. The predictive ability was validated by compounds that were not included in the training set. Furthermore, the CoMFA and CoMSIA model plots were mapped back to the binding sites of Checkpoint Kinase Weel, to get a better understanding of vital interactions between the inhibitors and Weel kinase. As a result, we have identified some key features in the 4-phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-diones responsible for the Weel inhibitory activity that may be used to design more potent 4-phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-diones and predict their activity prior to synthesis. SN - 0223-5234 UR - https://www.unboundmedicine.com/medline/citation/17698256/3D_QSAR_studies_of_Checkpoint_Kinase_Weel_inhibitors_based_on_molecular_docking_CoMFA_and_CoMSIA_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0223-5234(07)00265-6 DB - PRIME DP - Unbound Medicine ER -