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Comparative molecular field analysis and comparative molecular similarity indices analysis of boron-containing human thymidine kinase 1 substrates.
Bioorg Med Chem. 2006 Oct 15; 14(20):6924-32.BM

Abstract

Three-dimensional quantitative structure-activity relationship (3D-QSAR) using CoMFA and CoMSIA techniques was applied to evaluate 56 pyrimidine nucleosides as substrates of human thymidine kinase 1 (hTK1), 27 of them containing a carborane substituent either at the 3-, 5-, or 3'-position of the 2'-deoxyuridine scaffold. This is the first report describing 3D-QSAR studies of compounds containing boron atoms. Both CoMFA and CoMSIA models were derived from a training set of 47 molecules and the predictive capacity of the CoMSIA model was successfully validated by accurately calculating known phosphorylation rates of both boronated and non-boron hTK1 substrates that were not included in the training set. The optimal CoMSIA model provided the following values: q(2) 0.622, r(2) 0.983, s 0.165, and F 187.5. Contour maps obtained from the CoMSIA model were in agreement with the experimentally determined biological data.

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Authors+Show Affiliations

Bandyopadhyaya AK
Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA. bandyopadhyaya.1@osu.edu
Tiwari R
No affiliation info available
Tjarks W
No affiliation info available

MeSH

BoronHumansModels, MolecularMolecular StructureQuantitative Structure-Activity RelationshipStatic ElectricitySubstrate SpecificityThymidine Kinase

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

16828556

Citation

Bandyopadhyaya, Achintya K., et al. "Comparative Molecular Field Analysis and Comparative Molecular Similarity Indices Analysis of Boron-containing Human Thymidine Kinase 1 Substrates." Bioorganic & Medicinal Chemistry, vol. 14, no. 20, 2006, pp. 6924-32.
Bandyopadhyaya AK, Tiwari R, Tjarks W. Comparative molecular field analysis and comparative molecular similarity indices analysis of boron-containing human thymidine kinase 1 substrates. Bioorg Med Chem. 2006;14(20):6924-32.
Bandyopadhyaya, A. K., Tiwari, R., & Tjarks, W. (2006). Comparative molecular field analysis and comparative molecular similarity indices analysis of boron-containing human thymidine kinase 1 substrates. Bioorganic & Medicinal Chemistry, 14(20), 6924-32.
Bandyopadhyaya AK, Tiwari R, Tjarks W. Comparative Molecular Field Analysis and Comparative Molecular Similarity Indices Analysis of Boron-containing Human Thymidine Kinase 1 Substrates. Bioorg Med Chem. 2006 Oct 15;14(20):6924-32. PubMed PMID: 16828556.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparative molecular field analysis and comparative molecular similarity indices analysis of boron-containing human thymidine kinase 1 substrates. AU - Bandyopadhyaya,Achintya K, AU - Tiwari,Rohit, AU - Tjarks,Werner, Y1 - 2006/07/07/ PY - 2006/04/17/received PY - 2006/06/14/revised PY - 2006/06/19/accepted PY - 2006/7/11/pubmed PY - 2006/12/9/medline PY - 2006/7/11/entrez SP - 6924 EP - 32 JF - Bioorganic & medicinal chemistry JO - Bioorg Med Chem VL - 14 IS - 20 N2 - Three-dimensional quantitative structure-activity relationship (3D-QSAR) using CoMFA and CoMSIA techniques was applied to evaluate 56 pyrimidine nucleosides as substrates of human thymidine kinase 1 (hTK1), 27 of them containing a carborane substituent either at the 3-, 5-, or 3'-position of the 2'-deoxyuridine scaffold. This is the first report describing 3D-QSAR studies of compounds containing boron atoms. Both CoMFA and CoMSIA models were derived from a training set of 47 molecules and the predictive capacity of the CoMSIA model was successfully validated by accurately calculating known phosphorylation rates of both boronated and non-boron hTK1 substrates that were not included in the training set. The optimal CoMSIA model provided the following values: q(2) 0.622, r(2) 0.983, s 0.165, and F 187.5. Contour maps obtained from the CoMSIA model were in agreement with the experimentally determined biological data. SN - 0968-0896 UR - https://www.unboundmedicine.com/medline/citation/16828556/Comparative_molecular_field_analysis_and_comparative_molecular_similarity_indices_analysis_of_boron_containing_human_thymidine_kinase_1_substrates_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0968-0896(06)00502-5 DB - PRIME DP - Unbound Medicine ER -