258
Views
13
CrossRef citations to date
0
Altmetric
Original Articles

Pharmacophore mapping, molecular docking and QSAR studies of structurally diverse compounds as CYP2B6 inhibitors

&
Pages 887-905 | Received 02 Jan 2010, Accepted 28 Apr 2010, Published online: 15 Oct 2010

References

  • Nelson , D.R. , Koymans , L. , Kamataki , T. , Stegeman , J.J. , Feyereisen , R. , Waxman , D.J. , Waterman , M.R. , Gotoh , O. , Coon , M.J. , Estabrook , R.W. , Gunsalus , I.C. and Nebert , D.W. 1996 . P450 superfamily: Update on new sequences, gene mapping, accession numbers and nomenclature . Pharmacogenetics , 6 : 1 – 42 .
  • Nelson , D.R. , Zeldin , D.C. , Hoffman , S.M. , Maltais , L.J. , Wain , H.M. and Nebert , D.W. 2004 . Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice variants . Pharmacogenetics , 14 : 1 – 18 .
  • Nelson , D.R. 2005 . Gene nomenclature by default, or BLASTing to babel . Hum. Genomics , 2 : 196 – 201 .
  • Ekins , S. , Vandenbranden , M. , Ring , B.J. , Gillespie , J.S. , Yang , T.J. , Gelboin , H.V. and Wrighton , S.A. 1998 . Further characterization of the expression in liver and catalytic activity of CYP2B6 . J. Pharmacol. Exp. Ther. , 286 : 1253 – 1259 .
  • Gervot , L. , Rochat , B. , Gautier , J.C. , Bohnenstengel , F. , Kroemer , H. , de Berardinis , V. , Martin , H. , Beaune , P. and de Waziers , I. 1999 . Human CYP2B6: Expression, inducibility and catalytic activities . Pharmacogenetics , 9 : 295 – 306 .
  • Shimada , T. , Yamazaki , H. , Mimura , M. , Inui , Y. and Guengerich , F.P. 1994 . Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: Studies with liver microsomes of 30 Japanese and 30 caucasians . J. Pharmacol. Exp. Ther. , 270 : 414 – 423 .
  • Mimura , M. , Baba , T. , Yamazaki , H. , Ohmori , S. , Inui , Y. , Gonzalez , F.J. , Guengerich , F.P. and Shimada , T. 1993 . Characterization of cytochrome P450 2B6 in human liver microsomes . Drug Metab. Dispos. , 21 : 1048 – 1056 .
  • Stresser , D.M. and Kupfer , D. 1999 . Monospecific antipeptide antibody to cytochrome P-450 2B6 . Drug Metab. Dispos. , 27 : 517 – 525 .
  • Code , E.L. , Crespi , C.L. , Penman , B.W. , Gonzalez , F.J. , Chang , T.K. and Waxman , D.J. 1997 . Human cytochrome P4502B6: Interindividual hepatic expression, substrate specificity, and role in procarcinogen activation . Drug Metab. Dispos. , 2510 : 985 – 993 .
  • Bathelt , C. , Schmid , R.D. and Pleiss , J. 2002 . Regioselectivity of CYP2B6: Homology modeling, molecular dynamics simulation, docking . J. Mol. Model , 8 : 327 – 335 .
  • Hanna , H. , Reed , J.R. , Guengerich , F.P. and Hollenberg , P.F. 2000 . Expression of human cytochrome P450 2B6 in E. coli: Characterization of catalytic activity and expression levels in human liver . Arch. Biochem. Biophys. , 376 : 206 – 216 .
  • Hesse , L.M. , Venkatakrishnan , K. , Court , M.H. , von Moltke , L.L. , Duan , S.X. , Shader , R.I. and Greenblatt , D.J. 2000 . CYP2B6 mediates the in vitro hydroxylation of bupropion: Potential drug interactions with other antidepressants . Drug Metab. Dispos. , 28 : 1176 – 1183 .
  • Miksys , S. , Lerman , C. , Shields , P.G. , Mash , D.C. and Tyndale , R.F. 2003 . Smoking, alcoholism and genetic polymorphisms alter CYP2B6 levels in human brain . Neuropharmacology , 45 : 122 – 132 .
  • Nolan , D. , Phillips , E. and Mallal , S. 2006 . Efavirenz and CYP2B6 polymorphism: Implications for drug toxicity and resistance . Clin. Infect. Dis. , 42 : 408 – 410 .
  • Faucette , S.R. , Wang , H. , Hamilton , G.A. , Jolley , S.L. , Gilbert , D. , Lindley , C. , Yan , B. , Negishi , M. and LeCluyse , E. 2004 . Regulation of CYP2B6 in primary human hepatocytes by prototypical inducers . Drug Metab. Dispos. , 32 : 348 – 358 .
  • Walsky , R.L. , Astuccio , A.V. and Obach , R.S. 2006 . Evaluation of 227 drugs for in vitro inhibition of cytochrome P450 2B6 . J. Clin. Pharmacol. , 46 : 1426 – 1438 .
  • Turpeinen , M. , Raunio , H. and Pelkonen , O. 2006 . The functional role of CYP2B6 in human drug metabolism: Substrates and inhibitors in vitro, in vivo and in silico . Curr. Drug Metab. , 7 : 705 – 714 .
  • Svensson , U.S. and Ashton , M. 1999 . Identification of the human cytochrome P450 enzymes involved in the in vitro metabolism of artemisinin . Br. J. Clin. Pharmacol. , 48 : 528 – 535 .
  • Rotger , M. , Colombo , S. , Furrer , H. , Bleiber , G. , Buclin , T. , Lee , B.L. , Keiser , O. , Biollaz , J. , Decosterd , L. and Telenti , A. 2005 . Influence of CYP2B6 polymorphism on plasma and intracellular concentrations and toxicity of efavirenz and nevirapine in HIV-infected patients . Pharmacogenet. Genomics , 15 : 1 – 5 .
  • Coller , J.K. , Krebsfaenger , N. , Klein , K. , Endrizzi , K. , Wolbold , R. , Lang , T. , Nussler , A. , Neuhaus , P. , Zanger , U.M. , Eichelbaum , M. and Murdter , T.E. 2002 . The influence of CYP2B6, CYP2C9 and CYP2D6 genotypes on the formation of the potent antioestrogen Z-4-hydroxy-tamoxifen in human liver . Br. J. Clin. Pharmacol. , 54 : 157 – 167 .
  • Chang , T.K. , Weber , G.F. , Crespi , C.L. and Waxman , D.J. 1993 . Differential activation of cyclophosphamide and ifosphamide by cytochromes P-450 2B and 3A in human liver microsomes . Cancer Res. , 53 : 5629 – 5637 .
  • Mo , S.L. , Liu , Y.H. , Duan , W. , Wei , M.Q. , Kanwar , J.R. and Zhou , S.F. 2009 . Substrate specificity, regulation, and polymorphism of human cytochrome P450 2B6 . Curr. Drug Metab. ,
  • Wang , H. and Tompkins , L.M. 2008 . CYP2B6: New insights into a historically overlooked cytochrome P450 isozyme . Curr. Drug Metab. , 9 : 598 – 610 .
  • Kharasch , E.D. , Mitchell , D. and Coles , R. 2008 . Stereoselective bupropion hydroxylation as an in vivo phenotypic probe for cytochrome P4502B6 (CYP2B6) activity . J. Clin. Pharmacol. , 48 : 464 – 474 .
  • Walsky , R.L. , Astuccio , A.V. and Obach , R.S. 2006 . Evaluation of 227 drugs for in vitro inhibition of cytochrome P450 2B6 . J. Clin. Pharmacol. , 46 : 1426 – 1438 .
  • Kumagai , J. , Fujimura , T. , Takahashi , S. , Urano , T. , Ogushi , T. , Horie-Inoue , K. , Ouchi , Y. , Kitamura , T. , Muramatsu , M. , Blumberg , B. and Inoue , S. 2007 . Cytochrome P450 2B6 is a growth-inhibitory and prognostic factor for prostate cancer . Prostate , 67 : 1029 – 1037 .
  • Ekins , S. , Bravi , G. , Ring , B.J. , Gillespie , T.A. , Gillespie , J.S. , Vandenbranden , M. , Wrighton , S.A. and Wikel , J.H. 1999 . Three-dimensional quantitative structure–activity relationship analyses of substrates for CYP2B6 . J. Pharmacol. Exp. Ther. , 288 : 21 – 29 .
  • Wang , Q. and Halpert , J.R. 2002 . Combined 3D quantitative structure–activity relationship analysis of cytochrome P450 2B6 substrates and protein homology modeling . Drug Metab. Dispos. , 30 : 86 – 95 .
  • Lewis , D.F. , Lake , B.G. , Ito , Y. and Anzenbacher , P. 2006 . Quantitative structure–activity relationships (QSARs) within cytochromes P450 2B (CYP2B) subfamily enzymes: The importance of lipophilicity for binding and metabolism . Drug Metabol. Drug Interact. , 21 : 213 – 231 .
  • Korhonen , L.E. , Turpeinen , M. , Rahnasto , M. , Wittekindt , C. , Poso , A. , Pelkonen , O. , Raunio , H. and Juvonen , R.O. 2007 . New potent and selective cytochrome P450 2B6 (CYP2B6) inhibitors based on Three-dimensional and quantitative structure–activity relationship (3D-QSAR) analysis . Br. J. Pharmacol. , 150 : 932 – 942 .
  • Gay , S.C. , Shah , M.B. , Talakad , J.C. , Maekawa , K. , Roberts , A.G. , Wilderman , P.R. , Sun , L. , Yang , J.Y. , Huelga , S.C. , Hong , W.X. , Zhang , Q. , Stout , C.D. and Halpert , J.R. 2010 . Crystal structure of a cytochrome P450 2B6 genetic variant in complex with the inhibitor 4-(4-Chlorophenyl)imidazole at 2.0 Å resolution . Mol. Pharmacol. , 77 : 529 – 538 .
  • Discovery Studio 2.1 is a product of Accelrys Inc, San Diego, CA, USA.
  • Kurogi , Y. and Guner , O.F. 2001 . Pharmacophore modeling and Three-dimensional database searching for drug design using catalyst . Curr. Med. Chem. , 8 : 1035 – 1055 .
  • Debnath , A.K. 2002 . Pharmacophore mapping of a series of 2,4-diamino-5-deazapteridine inhibitors of mycobacterium avium complex dihydrofolate reductase . J. Med. Chem. , 45 : 41 – 53 .
  • Kahnberg , P. , Howard , M.H. , Liljefors , T. , Nielsen , M. , Nielsen , E.O. , Sterner , O. and Pettersson , I. 2004 . The use of a pharmacophore model for identification of novel ligands for the benzodiazepine binding site of the GABAA receptor . J Mol Graph Model , 23 : 253 – 261 .
  • Faragalla , J. , Bremner , J. , Brown , D. , Griffith , R. and Heaton , A. 2003 . Comparative pharmacophore development for inhibitors of human and rat 5-α-reductase . J. Mol. Graph. Model , 22 : 83 – 92 .
  • Ekins , S. , Bravi , G. , Wikel , J.H. and Wrighton , S.A. 1999 . Three-dimensional-quantitative structure–activity relationship analysis of cytochrome P-450 3A4 substrates . J. Pharmacol. Exp. Ther. , 291 : 424 – 433 .
  • Smellie , A. , Teig , S.L. and Towbin , P. 1995 . Poling: Promoting conformational variation . J. Comp. Chem. , 16 : 171 – 187 .
  • Kristam , R. , Gillet , V.J. , Lewis , R.A. and Thorner , D. 2005 . Comparison of conformational analysis techniques to generate pharmacophore hypotheses using catalyst . J. Chem. Inf. Model. , 45 : 461 – 476 .
  • Li , J. , Ehlers , T. , Sutter , J. , Varma-O'Brien , S. and Kirchmair , J. 2007 . CAESAR: A new conformer generation algorithm based on recursive buildup and local rotational symmetry consideration . J. Chem. Inf. Model. , 47 : 1923 – 1932 .
  • Hung , Y.H. and Liao , Y.S. 2008 . Applying PCA and fixed size LS-SVM method for large scale classification problems . Inf. Technol. J. , 7 : 890 – 896 .
  • Fawcett , T. 2006 . An introduction to ROC analysis . Pattern Recognit. Lett. , 27 : 861 – 874 .
  • Cerius2 version 4.10 is a product of Accelrys, Inc., San Diego, USA.
  • Leonard , J.T. and Roy , K. 2006 . On selection of training and test sets for the development of predictive QSAR models . QSAR Comb. Sci. , 25 : 235 – 251 .
  • Roy , K. and Mandal , A.S. 2008 . Development of linear and nonlinear predictive QSAR models and their external validation using molecular similarity principle for anti-HIV indolyl aryl sulfones . J. Enzyme Inhib. Med. Chem. , 23 : 980 – 995 .
  • Fan , Y. , Shi , L.M. , Kohn , K.W. , Pommier , Y. and Weinstein , J.N. 2001 . Quantitative structure-antitumor activity relationships of camptothecinanalogues: Cluster analysis and genetic algorithm-based studies . J. Med. Chem. , 44 : 3254 – 3263 .
  • Rogers , D. and Hopfinger , A.J. 1994 . Application of genetic function approximation to quantitative structure–activity relationship and quantitative structure–property relationship . J. Chem. Inf. Comput. Sci. , 34 : 854 – 866 .
  • Dunn III , W.J. and Rogers , D. 1996 . Genetic Partial Least Squares in QSAR, in Genetic Algorithms in Molecular Modeling , Edited by: Devillers , J. 109 – 130 . London : Academic Press .
  • Hasegawa , K. , Miyashita , Y. and Funatsu , K. 1997 . GA strategy for variable selection in QSAR studies: GA-based PLS analysis of calcium channel antagonists . J. Chem. Inf. Comput. Sci. , 37 : 306 – 310 .
  • Snedecor , G.W. and Cochran , W.G. 1967 . Statistical Methods , New Delhi : Oxford & IBH Publishing .
  • Wold , S. 1995 . PLS for Multivariate Linear Modeling, in Chemometric methods in molecular design , Edited by: van de Waterbeemd , H. 195 – 218 . Weinheim : VCH .
  • Debnath , A.K. 2001 . Quantitative structure–activity relationship (QSAR): A versatile tool in drug design, in Combinatorial Library Design and Evaluation: Principles, Software Tools, and Applications in Drug Discovery , Edited by: Ghose , A.K. and Viswanadhan , V.N. 73 – 129 . New York : Marcel Dekker .
  • Roy , K. 2007 . On some aspects of validation of predictive QSAR models . Expert. Opin. Drug. Discov. , 2 : 1567 – 1577 .
  • Roy , P.P. and Roy , K. 2008 . On some aspects of variable selection for partial least squares regression models . QSAR Comb. Sci. , 27 : 302 – 313 .
  • Roy , K. and Roy , P.P. 2008 . Comparative QSAR studies of CYP1A2 inhibitor flavonoids using 2D and 3D descriptors, Chem . Biol. Drug Des. , 72 : 370 – 382 .
  • Mitra , I. , Roy , P.P. , Kar , S. , Ojha , P. and Roy , K. 2010 . On further application of as a metric for validation of QSAR models . J. Chemometrics , 24 : 22 – 33 .
  • Roy , K. and Paul , S. 2008 . Exploring 2D and 3D QSARs of 2, 4-diphenyl-1, 3-oxazolines for ovicidal activity against tetranychus urticae . QSAR Comb. Sci. , 28 ( 4 ) : 406 – 425 .
  • Ekins , S. , Iyer , M. , Krasowski , M.D. and Kharasch , E.D. 2008 . Molecular characterization of cyp2b6 substrates . Curr. Drug Metab. , 9 : 363 – 373 .
  • Roy , P.P. , Leonard , J.T. and Roy , K. 2008 . Exploring the impact of the size of training sets for the development of predictive QSAR models . Chemom. Intell. Lab. Sys. , 90 : 31 – 42 .
  • Eriksson , L. , Jaworska , J. , Worth , A.P. , Cronin , M.T. , McDowell , R.M. and Gramatica , P. 2003 . Methods for reliability and uncertainty assessment and for applicability evaluations of classification- and regression-based QSARs . Environ. Health Perspect. , 111 : 1361 – 1375 .
  • Itokawa , D. , Nishioka , T. , Fukushima , J. , Yasuda , T. , Yamauchi , A. and Chuman , H. 2007 . Quantitative structure–activity relationship study of binding affinity of azole compounds with CYP2B and CYP3A . QSAR Comb. Sci. , 26 : 828 – 836 .

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.