Pharmacophore model of drugs involved in P-glycoprotein multidrug resistance: Explanation of structural variety (hypothesis)

Journal of Medicinal Chemistry

Volumn 45, Issue 26, 2002, Pages 5671-5686

  Pajeva, Ilza K ^a   Wiese, Michael ^b  

^a CENTRE OF BIOMEDICAL ENGINEERING   (Bulgaria)

^b UNIVERSITY OF BONN   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

AMIODARONE; CHLORPROMAZINE; GLYCOPROTEIN P; HALOPERIDOL; KETOCONAZOLE; METOPROLOL; NORVERAPAMIL; OMEPRAZOLE; PAFENOLOL; PROPAFENONE; PROPRANOLOL; QUINIDINE; RESERPINE; RHODAMINE 123; TAMOXIFEN; TRIFLUOPERAZINE; TRIFLUPROMAZINE; VERAPAMIL; VINBLASTINE;

ARTICLE; BINDING AFFINITY; BINDING SITE; DRUG CONFORMATION; DRUG STRUCTURE; GEOMETRY; HYDROGEN BOND; HYDROPHOBICITY; MOLECULAR INTERACTION; MOLECULAR MODEL; MULTIDRUG RESISTANCE; PHARMACOPHORE; PHYSICAL CHEMISTRY;

ADENOSINE TRIPHOSPHATASES; ALGORITHMS; ANTINEOPLASTIC AGENTS; BINDING SITES; BINDING, COMPETITIVE; CACO-2 CELLS; DRUG RESISTANCE, MULTIPLE; DRUG RESISTANCE, NEOPLASM; FLUORESCEINS; HUMANS; LIGANDS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; P-GLYCOPROTEIN; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP; RADIOLIGAND ASSAY; RHODAMINE 123; STEREOISOMERISM; VERAPAMIL; VINBLASTINE;

EID: 0037137614     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm020941h     Document Type: Article

References (51)

1. Ambudkar, S. V.; Dey, S.; Hrycyna, C. A.; Ramachandra, M.; Pastan, I.; Gottesman, M. Biochemical, Cellular, and Pharmacological aspects of the multidrug transporter. Annu. Rev. Pharmacol. Toxicol. 1999, 39, 361-398.
2. Pearce, H. L.; Safa, A. R.; Bach, N. J.; Winter, M. A.; Cirtain, M. C.; Beck, W. T. Essential features of the P-glycoprotein pharmacophore as defined by a series of reserpine analogs that modulate multidrug resistance. Proc. Natl. Acad. Sci. U.S.A. 1989, 86, 5128-5132.
3. Pearce, H. L.; Winter, M. A.; Beck, W. T. Structural characteristics of compounds that modulate P-glycoprotein-associated multidrug resistance. Adv. Enzyme Regul. 1990, 30, 357-373.
4. Hait, W. N.; Aftab, D. Rational design and pre-clinical pharmacology of drugs for reversing multidrug resistance. Biochem. Pharmacol. 1992, 43, 103-107.
5. Suzuki, T.; Fukazawa, N.; San-nohe, K. Structure-activity relationship of newly synthesized quinoline derivatives for reversal of multidrug resistance in cancer. J. Med. Chem. 1997, 40, 2047-2052.
6. Etievant, C.; Schambel, P.; Guminski, Y.; Barret, J.-M.; Imbert, T.; Hill, B. T. Requirements for P-glycoprotein recognition based on structure-activity relationships in the podophyllotoxin series. Anti-Cancer Drug Des. 1998, 13, 317-336.
7. Seelig, A. A General pattern for substrate recognition by P-glycoprotein. Eur. J. Biochem. 1998, 251, 252-261.
8. Wiese, M.; Pajeva, I. Structure-activity relationships of multi-drug resistance reversers. Curr. Med. Chem. 2001, 8, 685-713.
9. Zamora, J. M.; Pearce, H. L.; Beck, W. T. Physical-chemical properties shared by compounds that modulate multidrug resistance in human leukemic cells. Mol. Pharmacol. 1998, 33, 454-462.
10. Litman, T.; Zeuthen, T.; Skovsgaard, T.; Stein, W. D. Structure -Activity Relationships of P-Glycoprotein Interacting Drugs: Kinetic Characterization of Their Effects on ATPase Activity. Biochim. Biophys. Acta 1997, 1361, 159-168.
11. Doeppenschmitt, S.; Spahn-Langguth, H.; Regard, C. G.; Langguth, P. Radioligand-binding assay employing P-glycoprotein-overexpressing cells: Testing drug affinities to the secretory intestinal multidrug transporter. Pharm. Res. 1998, 15, 1001-1006.
12. Doeppenschmitt, S.; Langguth, P.; Regardh, C. G.; Andersson, T. B.; Hilgendorf, C.; Spahn-Langguth, H. Characterization of Binding Properties to human P-glycoprotein: Development of a [3H]Verapamil radioligand-binding assay. J. Pharmacol. Exp. Ther. 1999, 288, 348-357.
13. Doeppenschmitt, S.; Spahn-Langguth, H.; Regardh, C. G.; Langguth, P. Role of P-glycoprotein-mediated secretion in absorptive drug permeability: An approach using passive membrane permeability and affinity to P-glycoprotein. J. Pharm. Sci. 1999, 88, 1067-1072.
14. Neuhoff, S.; Langguth, P.; Dressier, C.; Andersson, T. B.; Regardh, C. G.; Spahn-Langguth, H. Affinities at the Verapamil binding site of MDR1-encoded P-glycoprotein: Drugs and analogs, stereoisomers and metabolites. Int. J. Clin. Pharm. Ther. 2000, 38, 168-179.
15. Jones, G.; Willett, P.; Glen, R. C. A genetic algorithm for flexible molecular overlay pharmacophore elucidation. J. Comput.-Aided Mol. Des. 1995, 9, 532-549.
16. Tiberghien, F.; Loor, F. Ranking of P-glycoprotein substrates and inhibitors by a calcein-am fluorometry screening assay. Anti-Cancer Drugs 1996, 7, 568-578.
17. Martindale, W. The Extra Pharmacopoeia/Martindale, 30th Ed.; Pharmaceutical Press: London, 1993.
18. Craig, P. N. Drug compendium. In Comprehensive Medicinal Chemistry; Hansch, C., Sammes, P. G., Taylor, J. B., Eds.; Pergamon: Oxford, 1990; Vol. 6, pp 237-991.
19. Franke, U.; Munk, A.; Wiese, M. Ionization constants and distribution coefficients of phenothiazines and calcium channel antagonists determined by a pH-metric method and correlation with calculated partition coefficients. J. Pharm. Sci. 1999, 88, 89-95.
20. Sybyl, Version 6.7; Tripos Inc., 1699 South Hanley Road, St. Louis, MO 63144-2917; October 2000.
21. URL: http://www.acdlabs.com. E-mail: robin.martin@acdlabs.com.
22. Safa, A. R. Photoaffinity labeling of the multidrug-resistance-related P-glycoprotein with photoactive analogs of Verapamil. Proc. Natl. Acad. Sci. U.S.A. 1988, 85, 7187-7191.
23. van der Sandt, I. C. J.; Blom-Roosemalen, M. C. M.; de Boer, A. G.; Breimer, D. D. Specificity of doxorubicin versus rhodamine-123 in assessing P-glycoprotein functionality in the LLC-PK1, LLC-PK1 MDR1 and Caco-2 cell lines. Eur. J. Pharm., Sci. 2000, 11, 207-214.
24. Österberg, T.; Norinder, U. Theoretical calculation and prediction of P-glycoprotein interacting drugs using MolSurf parametrization and PLS statistics. Eur. J. Pharm. Sci. 2000, 10, 295-303.
25. Martin, C.; Berridge, G.; Mistry, P.; Higgins, C.; Charlton, P.; Callaghan, R. Drug binding sites on P-glycoprotein are altered by ATP binding prior to nucleotide hydrolysis. Biochemistry 2000, 39, 11901-11906.
26. Julien, M.; Kajiji, S.; Kaback, R. H.; Gros, P. Simple purification of highly active biotinylated P-glycoprotein: Enantiomer-specific modulation of drug-stimulated ATPase activity. Biochemistry 2000, 39, 75-85.
27. Ford, J. M.; Prozialeck, W. C.; Hait, W. N. Structural features determining activity of phenothiazines and related drugs for inhibition of cell growth and reversal of multidrug resistance. Mol. Pharmacol. 1989, 35, 105-115.
28. Ford, J. M.; Bruggemann, E. P.; Pastan, I.; Gottesman, M. M.; Hait, W. N. Cellular and biochemical characterization of thioxanthenes for reversal of multidrug resistance in human and murine cell lines. Cancer Res. 1990, 50, 1748-1756.
29. Pajeva, I. K.; Wiese, M. Molecular modeling of phenothiazines and related drugs as multidrug resistance modifiers: A comparative molecular field analysis study. J. Med. Chem. 1998, 41, 1815-1826.
30. Pajeva, I. K.; Wiese, M. A comparative molecular field analysis of propafenone-type modulators of cancer multidrug resistance. Quant. Struct.-Act. Relat. 1998, 17, 301-312.
31. Pajeva, I. K.; Wiese, M. Multidrug resistance related drugs: Estimation of hydrophobicity as a space directed molecular property. C. R. Acad. Bulg. Sci. 2001, 54, 81-84.
32. Pajeva, I. K.; Wiese, M. Human P-glycoprotein pseudoreceptor modeling: 3D-QSAR study of thioxanthene type multidrug resistance modulators. Quant. Struct.-Act. Relat. 2001, 20, 130-138.
33. Raevsky, O. A. Quantification of non-covalent interaction on the basis of the thermodynamic hydrogen bond parameters. J. Phys. Org. Chem. 1997, 10, 405-413 (with special thanks to the help of Dr. K.-J. Schaper, Borstel Research Institute, Germany).
34. German, U. A. P-glycoprotein - A mediator of multidrug resistance in tumour cells. Eur. J. Cancer 1996, 32A, 927-944.
35. Ecker, G.; Huber, M.; Schmid, D.; Chiba, P. The importance of a nitrogen atom in modulators of multidrug resistance. Mol. Pharmacol. 1999, 56, 791-796.
36. Ecker, G. F.; Csaszar, E.; Kopp, S.; Plagens, B.; Holzer, W.; Ernst, W.; Chiba, P. Identification of ligand-binding regions of P-glycoprotein by activated-pharmacophore photoaffinity labeling and matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry. Mol. Pharmacol. 2002, 61, 637-648.
37. Frezard, F.; Pereira-Maia, E.; Quidu, P.; Priebe, W.; Garnier-Suillerot, A. P-glycoprotein preferentially effluxes anthracy-clines containing free basic versus charged amine. Eur. J. Biochem. 2001, 268, 1561-1567.
38. Ferry, D.; Boer, R.; Callaghan, R.; Ulrich, W.-R. Localization of the 1,4-dihydropyridine drug acceptor of P-glycoprotein to a cytoplasmic domain using a permanently charged derivative N-methyl dexniguldipine. Int. J. Clin. Pharmacol. Ther. 2000, 38, 130-140.
39. Schmid, D.; Ecker, G.; Kopp, S.; Hitzler, M.; Chiba, P. Structure-activity relationship studies of propafenone analogs based on P-glycoprotein ATPase activity measurements. Biochem. Pharmacol. 1999, 58, 1447-1456.
40. Martin, C.; Higgins, C. F.; Callaghan, R. The vinblastine binding site adopts high- and low-affinity conformations during a transport cycle of P-glycoprotein. Biochemistry 2001, 40, 15733-15742.
41. Seelig, A.; Landwojtowicz, E. Structure-activity relationship of P-glycoprotein substrates and modifiers. Eur. J. Pharm. Sci. 2000, 12, 31-40.
42. Penzoti, J. E.; Lamb, M. L.; Evensen, E.; Grootenhuis, P. D. J. A computational ensemble pharmacophore model for identifying substrates of P-glycoprotein. J. Med. Chem. 2002, 45, 1737-1740.
43. Scala, S.; Akhmed, N.; Rao, U. S.; Paull, K; Lan, L.-B.; Dickstein, B.; Lee, J.-S.; Elgemeie, G. H.; Stein, W. D.; Bates, S. E. P-glycoprotein substrates and antagonists cluster into two distinct groups. Mol. Pharmacol. 1997, 51, 1024-1033.
44. Ekins, S.; Kim, R. B.; Leake, B. F.; Dantzig, A. H.; Schuetz, E. G.; Lan, L.-B.; Yasuda, K.; Shepard, R. L.; Winter, M. A.; Schuetz, J. D.; Wikel, J. H.; Wrighton, S. A. Mol. Pharmacol. 2002, 61, 964-973.
45. Ekins, S.; Kim, R. B.; Leake, B. F.; Dantzig, A. H.; Schuetz, E. G.; Lan, L.-B.; Yasuda, K.; Shepard, R. L.; Winter, M. A.; Schuetz, J. D.; Wikel, J. H.; Wrighton, S. A. Mol. Pharmacol. 2002, 61, 974-981.
46. SYBYL/GASP Interface, Ligand-Based Design Manual, Version 6.7; Tripos, Inc., 1699 South Hanley Road, St. Louis, MO 63144-2917; October 2000.
47. ClogP for Windows, Version 1.0.0; BioByte Corp., 201 West 4th Street, Suite 204, Claremont, CA 91711; 1995.
48. Vazquez-Laslop, N.; Zheleznova, E. E.; Markham, P. N.; Brennan, R. G.; Neyfakh, A. A. Recognition of multiple drugs by a single protein: A trivial solution of an old paradox. Biochem. Soc. Trans. 2000, 28, 517-520.
49. Cambridge Structural Database, Version 5.20; Cambridge Crystallographic Data Center, 12 Union Road, Cambridge CB2 1EZ, U.K.
50. MOPAC 7 (QCPE No. 688): Department of Chemistry, Indiana University, Bloomington, IN 47405.
51. 2+complex. J. Med. Chem. 1993, 36, 1017-1023.