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In Silico Multivariate Regressio n Analysis and Validation Studies on Selective MMP-13 Inhibitors
| International Journal of Computer Applications |
| Foundation of Computer Science (FCS), NY, USA |
| Volume 130 - Number 6 |
| Year of Publication: 2015 |
| Authors: G. Nirmala, A. Yesubabu, P. Seetharamaiah |
10.5120/ijca2015907019
|
G. Nirmala, A. Yesubabu, P. Seetharamaiah . In Silico Multivariate Regressio n Analysis and Validation Studies on Selective MMP-13 Inhibitors. International Journal of Computer Applications. 130, 6 ( November 2015), 24-37. DOI=10.5120/ijca2015907019
Abstract
QSAR(Quantitative Structure Activity Relationship) studies were carried out on a set of 72 α-sulfone hydroxamatesas Matrix Metalloproteinase-13 (MMP-13) inhibitors using multiple regression procedure. Outliers were removed based on Relative Error calculation and Extent of Extrapolation. The activity contributions of these compounds were determined from regression equation and the validation procedures such as external set cross-validation r2, (R2cv, ext) and the regression of observed activities versus predicted activities and vice versa for validation set was described to analyze the predictive ability of the QSAR model. Parameters concerning predictive ability of QSAR model and Y-randomization tests were found to be within the limits. From a set of 5 models, an accurate and reliable QSAR model involving six descriptors was chosen based on the FIT Kubinyi function, which defines the statistical quality of the model. The generated model could be useful in designing more potent inhibitors of MMP-13.
References
- PD Brown, R Giavazzi, 1995 Matrixmetalloproteinase inhibition: A review of anti-tumour activity. Ann. Oncol. 6:967-974.
- J Gross, CM Lapiere. 1962 Collagenolytic activity in amohibian tissues - a tissue culture assay. Proc Natl Acad Sci USA 48:1014-1022
- P Vihinen, R Ala-aho, VM Kahari 2005 Matrix metalloproteinases as therapeutic targets in cancer. Curr. Cancer Drug Targets 5:203-220.
- Christian K. Engel 2005 Structural Basis for the Highly Selective Inhibition of MMP-13. Chemistry & Biology 12:181–189
- H Matter,M Schudok, 2004 Recent advances in the design of matrix metalloproteinase inhibitors. Curr. Opin. Drug Disc. Devel. 7:513–535.
- ZR Wasserman 2005 Chem. Biol. 12:143.
- Yvette M Fobian, John N Freskos, Thomas E Barta, Louis J Bedell, Robert Heintz, Darren J Kassab, James R Kiefer, Brent V Mischke, John M Molyneaux, Patrick Mullins, Grace E Munie, Daniel P Becker 2011 MMP-13 selective alpha-sulfone hydroxamates: Identification of selective P10 amides. Bioorganic & Medicinal Chemistry Letters 21:2823–2825.
- Johnson AR, Pavlovsky AG, Ortwine, DF, Prior F, Man CF, Bornemeier DA, Banotai CA, Mueller WT, McConnell P, Yan C, Baragi V, Lesch C, Roark WH, Wilson M, Datta K, Guzman R, Han HK, Dyer RD (2007) J. Biol Chem. 282:27781.
- Stephen A Kolodziej, Susan L Hockerman, Gary A DeCrescenzo, Joseph J McDonald, Debbie A Mischke, Grace E Munie, Theresa R Fletcher, Nathan Stehle, Craig Swearingen, Daniel P Becker 2010 MMP-13 selective isonipecotamide a-sulfone hydroxamates. Bioorganic & Medicinal Chemistry Letters 20:3561–3564.
- Stephen A Kolodziej, Susan L Hockerman, Terri L Boehm, Jeffery N Carroll, Gary A DeCrescenzo, Joseph J McDonald, Debbie A Mischke, Grace E Munie, Theresa R Fletcher, Joseph G Rico, Nathan W Stehle, Craig Swearingen, Daniel P Becker 2010 Orally bioavailable dual MMP-1/MMP-14 sparing, MMP-13 selective a-sulfone hydroxamates. Bioorganic & Medicinal Chemistry Letters 20:3557–3560
- Fobian YM, Freskos JN, Barta TE, Bedell LJ, Heintz R, Kassab DJ, Kiefer JR, Mischke BV, Molyneaux JM, Mullins P, Munie GE, Becker DP (2011) MMP-13 selective alpha-sulfone hydroxamates: identification of selective P1' amides. Bioorganic & Medicinal Chemistry Letters 21:2823–2825.
- Sharma BK, Singh P 2013 Chemometric Descriptor Based QSAR Rationales for the MMP-13 Inhibition Activity of Non-Zinc-Chelating Compounds. Med chem 3:168-178.
- G.B. Kulkarni, A. Siva Reddy, Konda Ramadevi, Devarapalli Kezia and M. Narasimha Rao 2009 3D-QSAR Studies of Matrix Metalloproteinase-13 Inhibitors. Rasayan J Chem. 2:407-414.
- BK Sharma, P Singh and YS Prabhakar 2013 QSAR rationale of Matrix metalloproteinase inhibition activity in a class of carboxylic acid based compounds. British Journal of Pharmaceutical Research 3:697-721.
- Michael Ferna´ndez and Julio Caballero 2007 QSAR modeling of matrix metalloproteinase inhibition by N-hydroxy-a-phenylsulfonylacetamide derivatives. Bioorganic & Medicinal Chemistry 15:6298–6310.
- Xi L, Li S, Yao X, Wei Y, Li J, Liu H, Wu 2014 In Silico Study Combining Docking and QSAR Methods on a Series of Matrix Metalloproteinase 13 Inhibitors. Arch. Pharm. doi: 10.1002/ardp.201400200.
- Golbraikh A, Tropsha A 2002 Beware of q2!. J. Mol. Graph. Model. 20:269-276.
- Afantitis A, Melagraki G, Sarimveis H, Koutentis PA, Markopoulos J, Igglessi-Markopoulou O 2006 A novel QSAR model for predicting induction of apoptosis by 4-aryl-4H-chromenes. Bioorg. Med. Chem. 14:6686-6694.
- Kim D, Hong S, Lee D 2006 The Quantitative Structure-Mutagenicity Relationship of Polycylic Aromatic Hydrocarbon Metabolites. Int. J. Mol. Sci. 7:556-570.
- Afantitis A, Melagraki G, Sarimveis H, Koutentis PA, Markopoulos J, Igglessi-Markopoulou O 2006 Investigation of substituent effect of 1-(3,3-diphenylpropyl)-piperidinyl phenylacetamides on CCR5 binding affinity using QSAR and virtual screening techniques. J. Comput. Aided Mol. Des. 20:83-95.
- Kubinyi H 1994 Variable selection in QSAR studies. II. A Highly Efficient Combination of Systematic Search and Evolution. Quant. Struct. Act. Relat. 13:393-401.
- Kubinyi H 1994 Variable selection in QSAR studies. I. An evolutionary algorithm. Quant. Struct. Act. Relat. 13:285-294.
- Hall LH, Mohney B, Kier LB 1991 The Electrotopological State: Structure Information at the Atomic Level for Molecular Graphs. J. Chem. Inf. Comput. Sci. 31:76-82
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