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3D-QSAR studies of boron-containing dipeptides as proteasome inhibitors with CoMFA and CoMSIA methods.
Eur J Med Chem. 2009 Apr; 44(4):1486-99.EJ

Abstract

Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were performed for a series of dipeptide boronate proteasome inhibitors using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) techniques. A training set containing 46 molecules served to establish the models. The optimum CoMFA and CoMSIA models obtained for the training set were all statistically significant with cross-validated coefficients (q(2)) of 0.676 and 0.630 and conventional coefficients (r(2)) of 0.989 and 0.956, respectively. The predictive capacities of both models were successfully validated by calculating a test set of 13 molecules that were not included in the training set. The predicted correlation coefficients (r(2)(pred)) of CoMFA and CoMSIA are 0.963 and 0.919, respectively. The CoMFA and CoMSIA field contour maps agree well with the structural characteristics of the binding pocket of beta5 subunit of 20S proteasome, which suggests that the 3D-QSAR models constructed in this paper can be used to guide the development of novel dipeptide boronate inhibitors of 20S proteasome.

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Authors+Show Affiliations

Zhu YQ
Jiangsu Simcere Pharmaceutical Research Institute, No. 699-18 Xuan Wu Avenue, Xuan Wu District, Nanjing 210042, PR China. zhuyongqiang@simcere.com
Lei M
No affiliation info available
Lu AJ
No affiliation info available
Zhao X
No affiliation info available
Yin XJ
No affiliation info available
Gao QZ
No affiliation info available

MeSH

BoronComputer SimulationDipeptidesDrug DesignEnzyme InhibitorsLigandsModels, MolecularMolecular ConformationProteasome InhibitorsQuantitative Structure-Activity Relationship

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18771818

Citation

Zhu, Yong-Qiang, et al. "3D-QSAR Studies of Boron-containing Dipeptides as Proteasome Inhibitors With CoMFA and CoMSIA Methods." European Journal of Medicinal Chemistry, vol. 44, no. 4, 2009, pp. 1486-99.
Zhu YQ, Lei M, Lu AJ, et al. 3D-QSAR studies of boron-containing dipeptides as proteasome inhibitors with CoMFA and CoMSIA methods. Eur J Med Chem. 2009;44(4):1486-99.
Zhu, Y. Q., Lei, M., Lu, A. J., Zhao, X., Yin, X. J., & Gao, Q. Z. (2009). 3D-QSAR studies of boron-containing dipeptides as proteasome inhibitors with CoMFA and CoMSIA methods. European Journal of Medicinal Chemistry, 44(4), 1486-99. https://doi.org/10.1016/j.ejmech.2008.07.019
Zhu YQ, et al. 3D-QSAR Studies of Boron-containing Dipeptides as Proteasome Inhibitors With CoMFA and CoMSIA Methods. Eur J Med Chem. 2009;44(4):1486-99. PubMed PMID: 18771818.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 3D-QSAR studies of boron-containing dipeptides as proteasome inhibitors with CoMFA and CoMSIA methods. AU - Zhu,Yong-Qiang, AU - Lei,Meng, AU - Lu,Ai-Jun, AU - Zhao,Xin, AU - Yin,Xiao-Jin, AU - Gao,Qing-Zhi, Y1 - 2008/07/24/ PY - 2008/06/13/received PY - 2008/07/09/revised PY - 2008/07/11/accepted PY - 2008/9/6/pubmed PY - 2009/7/2/medline PY - 2008/9/6/entrez SP - 1486 EP - 99 JF - European journal of medicinal chemistry JO - Eur J Med Chem VL - 44 IS - 4 N2 - Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were performed for a series of dipeptide boronate proteasome inhibitors using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) techniques. A training set containing 46 molecules served to establish the models. The optimum CoMFA and CoMSIA models obtained for the training set were all statistically significant with cross-validated coefficients (q(2)) of 0.676 and 0.630 and conventional coefficients (r(2)) of 0.989 and 0.956, respectively. The predictive capacities of both models were successfully validated by calculating a test set of 13 molecules that were not included in the training set. The predicted correlation coefficients (r(2)(pred)) of CoMFA and CoMSIA are 0.963 and 0.919, respectively. The CoMFA and CoMSIA field contour maps agree well with the structural characteristics of the binding pocket of beta5 subunit of 20S proteasome, which suggests that the 3D-QSAR models constructed in this paper can be used to guide the development of novel dipeptide boronate inhibitors of 20S proteasome. SN - 1768-3254 UR - https://www.unboundmedicine.com/medline/citation/18771818/3D_QSAR_studies_of_boron_containing_dipeptides_as_proteasome_inhibitors_with_CoMFA_and_CoMSIA_methods_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0223-5234(08)00340-1 DB - PRIME DP - Unbound Medicine ER -