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3D-QSAR and molecular docking studies of 2-pyrimidinecarbonitrile derivatives as inhibitors against falcipain-3.
Bioorg Med Chem Lett. 2011 Dec 01; 21(23):7219-23.BM

Abstract

The three dimensional-quantitative structure activity relationship (3D-QSAR) studies were performed on a series of falcipain-3 inhibitors using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) techniques. A training set containing 42 molecules served to establish the QSAR models. The optimum CoMFA and CoMSIA models obtained for the training set were statistically significant with cross-validated correlation coefficients r(cv)(2) (q(2)) of 0.549 and 0.608, and conventional correlation coefficients (r(2)) of 0.976 and 0.932, respectively. An independent test set of 12 molecules validated the external predictive power of both models with predicted correlation coefficients (r(pred)(2)) for CoMFA and CoMSIA as 0.697 and 0.509, respectively. The docking of inhibitors into falcipain-3 active site using GOLD software revealed the vital interactions and binding conformation of the inhibitors. The CoMFA and CoMSIA field contour maps agree well with the structural characteristics of the binding pocket of falcipain-3 active site, which suggests that the information rendered by 3D-QSAR models and the docking interactions can provide guidelines for the development of improved falcipain-3 inhibitors.

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Authors+Show Affiliations

Potshangbam AM
School of Chemistry, University of Hyderabad, Hyderabad, India.
Tanneeru K
No affiliation info available
Reddy BM
No affiliation info available
Guruprasad L
No affiliation info available

MeSH

Catalytic DomainCysteine EndopeptidasesEnzyme ActivationEnzyme InhibitorsModels, MolecularNitrilesPyrimidinesQuantitative Structure-Activity Relationship

Pub Type(s)

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

Language

eng

PubMed ID

22018459

Citation

Potshangbam, Angamba Meetei, et al. "3D-QSAR and Molecular Docking Studies of 2-pyrimidinecarbonitrile Derivatives as Inhibitors Against Falcipain-3." Bioorganic & Medicinal Chemistry Letters, vol. 21, no. 23, 2011, pp. 7219-23.
Potshangbam AM, Tanneeru K, Reddy BM, et al. 3D-QSAR and molecular docking studies of 2-pyrimidinecarbonitrile derivatives as inhibitors against falcipain-3. Bioorg Med Chem Lett. 2011;21(23):7219-23.
Potshangbam, A. M., Tanneeru, K., Reddy, B. M., & Guruprasad, L. (2011). 3D-QSAR and molecular docking studies of 2-pyrimidinecarbonitrile derivatives as inhibitors against falcipain-3. Bioorganic & Medicinal Chemistry Letters, 21(23), 7219-23. https://doi.org/10.1016/j.bmcl.2011.09.107
Potshangbam AM, et al. 3D-QSAR and Molecular Docking Studies of 2-pyrimidinecarbonitrile Derivatives as Inhibitors Against Falcipain-3. Bioorg Med Chem Lett. 2011 Dec 1;21(23):7219-23. PubMed PMID: 22018459.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 3D-QSAR and molecular docking studies of 2-pyrimidinecarbonitrile derivatives as inhibitors against falcipain-3. AU - Potshangbam,Angamba Meetei, AU - Tanneeru,Karunakar, AU - Reddy,Bandi Madhusudhan, AU - Guruprasad,Lalitha, Y1 - 2011/10/01/ PY - 2011/06/14/received PY - 2011/09/07/revised PY - 2011/09/10/accepted PY - 2011/10/25/entrez PY - 2011/10/25/pubmed PY - 2012/4/19/medline SP - 7219 EP - 23 JF - Bioorganic & medicinal chemistry letters JO - Bioorg Med Chem Lett VL - 21 IS - 23 N2 - The three dimensional-quantitative structure activity relationship (3D-QSAR) studies were performed on a series of falcipain-3 inhibitors using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) techniques. A training set containing 42 molecules served to establish the QSAR models. The optimum CoMFA and CoMSIA models obtained for the training set were statistically significant with cross-validated correlation coefficients r(cv)(2) (q(2)) of 0.549 and 0.608, and conventional correlation coefficients (r(2)) of 0.976 and 0.932, respectively. An independent test set of 12 molecules validated the external predictive power of both models with predicted correlation coefficients (r(pred)(2)) for CoMFA and CoMSIA as 0.697 and 0.509, respectively. The docking of inhibitors into falcipain-3 active site using GOLD software revealed the vital interactions and binding conformation of the inhibitors. The CoMFA and CoMSIA field contour maps agree well with the structural characteristics of the binding pocket of falcipain-3 active site, which suggests that the information rendered by 3D-QSAR models and the docking interactions can provide guidelines for the development of improved falcipain-3 inhibitors. SN - 1464-3405 UR - https://www.unboundmedicine.com/medline/citation/22018459/3D_QSAR_and_molecular_docking_studies_of_2_pyrimidinecarbonitrile_derivatives_as_inhibitors_against_falcipain_3_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0960-894X(11)01351-5 DB - PRIME DP - Unbound Medicine ER -