Comparative molecular field analysis (CoMFA) and docking studies of non-nucleoside HIV-1 RT inhibitors (NNIs).
作者： M.L. Barreca , A. Carotti , A. Carrieri , A. Chimirri , A.M. Monforte
DOI: 10.1016/S0968-0896(99)00181-9
关键词: Field analysis 、 Molecular model 、 Docking (molecular) 、 Lipophilicity 、 Human immunodeficiency virus (HIV) 、 Nucleoside 、 Stereochemistry 、 Inhibitory potency 、 Steric effects 、 Chemistry
摘要: Abstract A set of TIBO derivatives endowed with reverse transcriptase (RT) inhibitory activity were analyzed by comparative molecular field analysis (CoMFA). Besides conventional steric and electrostatic fields, lipophilicity potential (MLP) was also used as a third in CoMFA. An informative statistically significant model ( q 2 =0.70, r =0.90, s =0.46) obtained taking into account the three types together. The key determinants governing RT inhibition congeners detected at 3-D level careful CoMFA isocontour maps. To challenge predictive ability model, an external thiazolobenzimidazole (TBZ) examined. Good predictions, suggesting similar binding mode for TBZ derivatives, emerged. Flexible docking experiments on TBZ, other NNIs confirmed common characteristics, found out CoMFA, moreover good correlation between calculated energies potency found.
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sci-hub.se 参考文章(28)
Colin Mcmartin, Regine S. Bohacek, QXP: powerful, rapid computer algorithms for structure-based drug design. Journal of Computer-aided Molecular Design. ,vol. 11, pp. 333- 344 ,(1997) , 10.1023/A:1007907728892
Bernard Testa, Pierre‐Alain Carrupt, Patrick Gaillard, Frédéric Billois, Peter Weber, Lipophilicity in molecular modeling Pharmaceutical Research. ,vol. 13, pp. 335- 343 ,(1996) , 10.1023/A:1016024005429
Chris Tantillo, Jianping Ding, Alfredo Jacobo-Molina, Raymond G. Nanni, Paul L. Boyer, Stephen H. Hughes, Rudi Pauwels, Koen Andries, Paul A.J. Janssen, Edward Arnold, Locations of anti-AIDS drug binding sites and resistance mutations in the three-dimensional structure of HIV-1 reverse transcriptase. Implications for mechanisms of drug inhibition and resistance Journal of Molecular Biology. ,vol. 243, pp. 369- 387 ,(1994) , 10.1006/JMBI.1994.1665
A. Carrieri, L. Brasili, F. Leonetti, M. Pigini, M. Giannella, P. Bousquet, A. Carotti, 2-D and 3-D modeling of imidazoline receptor ligands: Insights into pharmacophore Bioorganic & Medicinal Chemistry. ,vol. 5, pp. 843- 856 ,(1997) , 10.1016/S0968-0896(97)00023-0
W. J. Dunn, S. Wold, U. Edlund, S. Hellberg, J. Gasteiger, Multivariate structure‐activity relationships between data from a battery of biological tests and an ensemble of structure descriptors: The PLS method Quantitative Structure-activity Relationships. ,vol. 3, pp. 131- 137 ,(1984) , 10.1002/QSAR.19840030402
Patrick Gaillard, Pierre-Alain Carrupt, Bernard Testa, Alain Boudon, Molecular Lipophilicity Potential, a tool in 3D QSAR: Method and applications Journal of Computer-Aided Molecular Design. ,vol. 8, pp. 83- 96 ,(1994) , 10.1007/BF00119860
Scott J. Weiner, Peter A. Kollman, David A. Case, U. Chandra Singh, Caterina Ghio, Guliano Alagona, Salvatore Profeta, Paul Weiner, A NEW FORCE FIELD FOR MOLECULAR MECHANICAL SIMULATION OF NUCLEIC ACIDS AND PROTEINS Journal of the American Chemical Society. ,vol. 106, pp. 765- 784 ,(1984) , 10.1021/JA00315A051
Jianping Ding, Kalyan Das, Henri Moereels, Luc Koymans, Koen Andries, Paul A.J. Janssen, Stepen H. Hughes, Edward Arnold, Structure of HIV-1 RT/TIBO R 86183 complex reveals similarity in the binding of diverse nonnucleoside inhibitors Nature Structural & Molecular Biology. ,vol. 2, pp. 407- 415 ,(1995) , 10.1038/NSB0595-407
Michael J. Kukla, Henry J. Breslin, Craig J. Diamond, Philip P. Grous, Chih Y. Ho, Milton Miranda, James D. Rodgers, Ronald G. Sherrill, Erik De Clercq, Rudi Pauwels, Koen Andries, Luc J. Moens, Marcel A. C. Janssen, Paul A. J. Janssen, Synthesis and anti-HIV-1 activity of 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin- 2(1H)-one (TIBO) derivatives. Journal of Medicinal Chemistry. ,vol. 34, pp. 746- 751 ,(1991) , 10.1021/JM00115A007
R. A. Laskowski, M. W. MacArthur, D. S. Moss, J. M. Thornton, PROCHECK: a program to check the stereochemical quality of protein structures Journal of Applied Crystallography. ,vol. 26, pp. 283- 291 ,(1993) , 10.1107/S0021889892009944