Group-based QSAR and molecular dynamics mechanistic analysis revealing the mode of action of novel piperidinone derived protein-protein inhibitors of p53-MDM2

Journal of Molecular Graphics and Modelling

Volumn 51, Issue , 2014, Pages 64-72

  Goyal, Sukriti ^a   Grover, Sonam ^b   Dhanjal, Jaspreet Kaur ^b   Tyagi, Chetna ^b   Goyal, Manisha ^a   Grover, Abhinav ^b  

^a BANASTHALI UNIVERSITY   (India)

^b JAWAHARLAL NEHRU UNIVERSITY   (India)

Author keywords

Cancer; Library; MDM2; p53; Piperidinone; QSAR

Indexed keywords

BINDING ENERGY; CELL DEATH; DISEASES; FEEDBACK; LEAD COMPOUNDS; LIBRARIES; MOLECULAR DYNAMICS; MOLECULAR GRAPHICS; PROTEINS; STATISTICAL TESTS; TUMORS; UNSATURATED COMPOUNDS;

CANCER; DESIGN AND DEVELOPMENT; MDM2; MOLECULAR DYNAMICS SIMULATIONS; NEGATIVE FEEDBACK REGULATORS; PIPERIDINONE; QSAR; STATISTICAL PARAMETERS;

COMPUTATIONAL CHEMISTRY;

PIPERIDONE DERIVATIVE; PROTEIN MDM2; PROTEIN P53; ANTINEOPLASTIC AGENT; PIPERIDINE DERIVATIVE; PROTEIN BINDING;

ARTICLE; BINDING AFFINITY; COMBINATORIAL LIBRARY; CORRELATION COEFFICIENT; DRUG STRUCTURE; HYDROGEN BOND; MOLECULAR DYNAMICS; PRIORITY JOURNAL; PROTEIN PROTEIN INTERACTION; QUANTITATIVE STRUCTURE ACTIVITY RELATION; STATISTICAL PARAMETERS; ANTAGONISTS AND INHIBITORS; BINDING SITE; CHEMICAL PHENOMENA; CHEMISTRY; HUMAN; MOLECULAR DOCKING; PROTEIN DOMAIN;

ANTINEOPLASTIC AGENTS; BINDING SITES; HUMANS; HYDROGEN BONDING; HYDROPHOBIC AND HYDROPHILIC INTERACTIONS; MOLECULAR DOCKING SIMULATION; MOLECULAR DYNAMICS SIMULATION; PIPERIDINES; PROTEIN BINDING; PROTEIN INTERACTION DOMAINS AND MOTIFS; PROTO-ONCOGENE PROTEINS C-MDM2; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP; TUMOR SUPPRESSOR PROTEIN P53;

EID: 84901256685     PISSN: 10933263     EISSN: 18734243     Source Type: Journal    
DOI: 10.1016/j.jmgm.2014.04.015     Document Type: Article

References (22)

1. B. Peter, and L. Bernard World Cancer Report 2008 WHO
2. R. Siegel, D. Naishadham, and A. Jemal Cancer statistics CA. Cancer J. Clin. 62 2012 10 29
3. M.M. Gottesman Mechanisms of cancer drug resistance Annu. Rev. Med. 53 2002 615 627 (Pubitemid 34177898)
4. S. Ajmani, K. Jadhav, and S.A. Kulkarni Group-based QSAR (G-QSAR): mitigating interpretation challenges in QSAR QSAR Comb. Sci. 28 2009 36 51
5. M. Barinaga Designing therapies that target tumor blood vessels Science 275 1997 482 484 (Pubitemid 27051889)
6. F. Toledo, C.J. Lee, K.A. Krummel, L.-W. Rodewald, C.-W. Liu, and G.M. Wahl Mouse mutants reveal that putative protein interaction sites in the p53 proline-rich domain are dispensable for tumor suppression Mol. Cell. Biol. 27 2007 1425 1432 (Pubitemid 46239823)
7. J.S. Fridman, and S.W. Lowe Control of apoptosis by p53 Oncogene 22 2003 9030 9040 (Pubitemid 38121703)
8. K.H. Vousden, and X. Lu Live or let die: the cell's response to p53 Nat. Rev. Cancer 2 2002 594 604 (Pubitemid 37328926)
9. L.T. Vassilev, B.T. Vu, B. Graves, D. Carvajal, F. Podlaski, Z. Filipovic, N. Kong, U. Kammlott, C. Lukacs, and C. Klein In vivo activation of the p53 pathway by small-molecule antagonists of MDM2 Sci. Signal. 303 2004 844
10. J.G. Allen, M.P. Bourbeau, G.E. Wohlhieter, M.D. Bartberger, K. Michelsen, R. Hungate, R.C. Gadwood, R.D. Gaston, B. Evans, and L.W. Mann Discovery and optimization of chromenotriazolopyrimidines as potent inhibitors of the mouse double minute 2-tumor protein 53 protein-protein interaction J. Med. Chem. 52 2009 7044 7053
11. H.P. Beck, M. DeGraffenreid, B. Fox, J.G. Allen, Y. Rew, S. Schneider, A.Y. Saiki, D. Yu, J.D. Oliner, and K. Salyers Improvement of the synthesis and pharmacokinetic properties of chromenotriazolopyrimidine MDM2-p53 protein-protein inhibitors Bioorg. Med. Chem. Lett. 21 2011 2752 2755
12. P.H. Kussie, S. Gorina, V. Marechal, B. Elenbaas, J. Moreau, A.J. Levine, and N.P. Pavletich Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain Science 274 1996 948 953 (Pubitemid 26398409)
13. Y. Rew, D. Sun, F. Gonzalez-Lopez De Turiso, M.D. Bartberger, H.P. Beck, J. Canon, A. Chen, D. Chow, J. Deignan, and B.M. Fox Structure-based design of novel inhibitors of the MDM2-p53 interaction J. Med. Chem. 55 2012 4936 4954
14. P. Csizmadia MarvinSketch and MarvinView: molecule applets for the World Wide Web Proceedings of ECSOC-3, the Third International Electronic Conference on Synthetic Organic Chemistry 1999 367 369
15. Vlife MDS, Software Package, Version 3.0 2008 Vlifescience Technologies Pvt. Ltd. Pune
16. A. Golbraikh, and A. Tropsha Beware of q2! J. Mol. Graphics Modell. 20 2002 269 276
17. A. Afantitis, G. Melagraki, H. Sarimveis, O. Igglessi-Markopoulou, and G. Kollias A novel QSAR model for predicting the inhibition of CXCR3 receptor by 4-N-aryl-[14] diazepane ureas Eur. J. Med. Chem. 44 2009 877 884
18. S. Izrailev, and D. Agrafiotis A novel method for building regression tree models for QSAR based on artificial ant colony systems J. Chem. Inf. Comput. Sci. 41 2001 176 180 (Pubitemid 33645687)
19. L. Schrödinger Schrodinger suite, Maestro Version 8 2008
20. N. Foloppe, and A.D. MacKerell Jr. All-atom empirical force field for nucleic acids: I. Parameter optimization based on small molecule and condensed phase macromolecular target data J. Comput. Chem. 21 2000 86 104
21. Schrodinger Schrodinger Suite 2009 Maestro LLC New York, NY
22. F. Gonzalez-Lopez de Turiso, D. Sun, Y. Rew, M.D. Bartberger, H.P. Beck, J. Canon, A. Chen, D. Chow, T.L. Correll, and X. Huang Rational design and binding mode duality of MDM2-p53 inhibitorsJ Med. Chem. 56 2013 4053 4070