Cyclosporins: Structure-activity relationships for the inhibition of the human MDR1 P-glycoprotein ABC transporter

Journal of Medicinal Chemistry

Volumn 45, Issue 21, 2002, Pages 4598-4612

  Loor, Francis ^a   Tiberghien, Françoise ^a,b   Wenandy, Tom ^a   Didier, Agnès ^a   Traber, René ^c  

^a UNIVERSITÉ DE STRASBOURG   (France)

^b Pole API   (France)

^c NOVARTIS PHARMA AG   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

ABC TRANSPORTER; CALCEIN; CYCLOPHILIN; CYCLOSPORIN A; CYCLOSPORIN DERIVATIVE; CYCLOSPORIN H; FR 901459; GLYCOPROTEIN P; MULTIDRUG RESISTANCE PROTEIN 1; SDZ 214 103; SDZ 214103; UNCLASSIFIED DRUG;

ARTICLE; BINDING AFFINITY; CANCER CELL; CONCENTRATION RESPONSE; DOSE RESPONSE; DRUG BINDING SITE; DRUG CONFORMATION; DRUG PROTEIN BINDING; HUMAN; HUMAN CELL; HYDROPHOBICITY; IC 50; METHYLATION; PROTEIN DOMAIN; STRUCTURE ACTIVITY RELATION;

ANTIBIOTICS, ANTIFUNGAL; CYCLOSPORINE; CYCLOSPORINS; HUMANS; IMMUNOSUPPRESSIVE AGENTS; MOLECULAR CONFORMATION; P-GLYCOPROTEIN; STRUCTURE-ACTIVITY RELATIONSHIP; TUMOR CELLS, CULTURED;

EID: 0037057583     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm0109863     Document Type: Article

References (58)

1. Dreyfuss, M. M.; Chapela, I. H. Potential of fungi in the discovery of novel, low-molecular weight pharmaceuticals. In The Discovery of Natural Products with Therapeutic Potential; Gullo, V. P., Ed.; Butterworth-Heinemann, Boston, 1994; pp 49-80.
2. Borel, J. F.; Baumann, G.; Chapman, I.; Donatsch, P.; Fähr, A.; Mueller, E. A.; Vigouret, J. M. In vivo pharmacological effects of ciclosporin and some analogues. Adv. Pharmacol. 1996, 33, 115-246.
3. Hiestand, P.; Gubler, H. U. Cyclosporins: Immunopharmacologic properties of natural cyclosporins. Handb. Exptl. Pharmacol. 1988, 85, 487-502.
4. Schreiber, S. L.; Crabtree, G. R. The mechanism of action of cyclosporin A and FK506. Immunol. Today 1992, 13, 136-142.
5. Sherry, B.; Yarlett, N.; Strupp, A.; Cerami, A. Identification of cyclophilin as a proinflammatory secretory product of lipopolysaccharide-activated macrophages. Proc. Natl. Acad. Sci. U.S.A. 1992, 89, 3511-3515.
6. Billich, A.; Hammerschmid, F.; Peichl, P.; Wenger, R.; Zenke, G.; Quesniaux, V.; Rosenwirth, B. Mode of action of SDZ NIM 811, a nonimmunosuppressive Cyclosporin A analogue with activity against human immunodeficiency virus (HIV) type 1: interference with HIV protein-cyclophilin A interactions. J. Virol. 1995, 69, 2451-2461.
7. Crompton, M. The mitochondrial permeability transition pore and its role in cell death. Biochem. J. 1999, 341, 233-249.
8. Lo Russo, A. L.; Passaquin, A. C.; André, P.; Skutella, M.; Rüegg, U. T. Effect of cyclosporin A and analogues on cytosolic calcium and vasoconstriction: possible lack of relationship to immuno-suppressive activity. Br. J. Pharmacol. 1996, 118, 885-892.
9. 1) receptor antagonist. Eur. J. Pharmacol. 1995, 289, 439-446.
10. Wenzel-Seifert, K.; Seifert, R. Cyclosporin H is a potent and selective formyl peptide receptor antagonist. Comparison with N-tert-butoxycarbonyl-L-phenylalanyl-L-leucyl- L-phenylalanyl-L-leucyl-L-phenylalanine and cyclosporins A, B, C, D, and E. J. Immunol. 1993, 150, 4591-4599.
11. Loor, F. Cyclosporins and related fungal products in the reversal of P-glycoprotein-mediated multidrug resistance. In Multidrug Resistance in Cancer Cells; Gupta, S., Tsuruo, T., Eds.; John Wiley & Sons Ltd.: Chichester, 1996; pp 387-412.
12. Van Helvoort, A.; Smith, A. J.; Sprong, H.; Fritzsche, I.; Schinkel, A. H.; Borst, P.; Van Meer, G. MDR1 P-glycoprotein is a lipid translocase of broad specificity, while MDR3 P-glycoprotein specifically translocates phosphatidylcholine. Cell 1996, 87, 507-517.
13. Gavériaux, C.; Boesch, D.; Boelsterli, J. J.; Bollinger, P.; Eberle, M. K.; Hiestand, P.; Payne, T.; Traber, R.; Wenger, R.; Loor, F. Overcoming multidrug resistance in Chinese hamster ovary cells in vitro by cyclosporin A (Sandimmune) and nonimmunosuppressive derivatives. Br. J. Cancer 1989, 60, 867-871.
14. Gavériaux, C.; Boesch, D.; Jachez, B.; Bollinger, P.; Payne, T.; Loor, F. SDZ PSC 833, a nonimmunosuppressive cyclosporin analogue, is a very potent multidrug-resistance modifier. J. Cell. Pharmacol. 1991, 2, 225-234.
15. Loor, F. Valspodar: current status and perspectives. Exp. Opin. Invest. Drugs 1999, 8, 807-835.
16. Vickers, A. E. M.; Alegret, M.; Jiménez, R. M.; Pflimlin, V.; Fisher, R.; Spaans, C.; Brendel, K. Changes in human liver and kidney slice function related to potential side-effects in the presence of biotransformation of four cyclosporin derivatives-CsA, IMM, OG, and PSC. In Vitro Mol. Toxicol. 1998, 11, 119-132.
17. Fähr, A. Cyclosporin clinical pharmacokinetics. Clin. Pharmacokinet. 1993, 24, 472-495.
18. Hamilton, G. S.; Steiner, J. P. Immunophilins: Beyond immunosuppression. J. Med. Chem. 1998, 41, 5119-5143.
19. 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.
20. Von Wartburg, A.; Traber, R. Chemistry of the natural cyclosporin metabolites. Prog. Allergy 1986, 38, 28-45.
21. Dreyfuss, M. M.; Schreier, M. H.; Tscherter, H.; Wenger, R. Cyclosporin peptolides, their preparation by fermentation or chemical synthesis and their use as pharmaceuticals. European Patent Application 0296 123 A2 (15.06.1988); Chem. Abstr. 1989, 111, 152146a.
22. Sakamoto, K.; Tsujii, E.; Miyauchi, M.; Nakanishi, T.; Yamashita, M.; Shigematsu, N.; Tada, T.; Izumi, S.; Okuhara, M. FR901459, a novel immunosuppressant isolated from Stachybotrys chartarum no. 19392. Taxonomy of the producing organism, fermentation, isolation, physicochemical properties and biological activities. J. Antibiot. 1993, 46, 1788-1798.
23. Jegorov, A.; Matha, V.; Sedmera, P.; Havlicek, V.; Stuchlik, J.; Seidel, P.; Simek, P. Cyclosporins from Tolypocladium terricola. Phytochemistry 1995, 38, 403-407.
24. Traber, R.; Dreyfuss, M. M. Occurrence of cyclosporins and cyclosporin-like peptolides in fungi. J. Ind. Microbiol. 1996, 17, 397-401.
25. Traber, R. Biosynthesis of cyclosporins. Biotechnology of Antibiotics, 2nd ed.; Strohl, W.R., Ed.; Dekker: New York, 1997; pp 279-313.
26. Traber, R.; Hofmann, H.; Kobel, H. Cyclosporins - New analogues by precursor directed biosynthesis. J. Antibiot. 1989, 42, 591-597.
27. 10]-cyclosporin, a cyclosporin related peptolide, with immunosuppressive activity by a multienzyme polypeptide. J. Biol. Chem. 1991, 265, 11355-11360.
28. Kuhnt, M.; Bitsch, F.; France, J.; Hofmann, H.; Sanglier, J. J.; Traber, R. Microbial biotransformation Products of Cyclosporin A. J. Antibiot. 1996, 49, 781-787.
29. Wenger, R. M. Synthesis of ciclosporin and analogues: structural and conformational requirements for immunosuppressive activity. Prog. Allergy 1986, 38, 46-64.
30. Wenger, R. M. Cyclosporine: Conformation and analogues as tools for studying its mechanism of action. Transplant. Proc. 1988, XX, 313-318.
31. Walkinshaw, M. D.; Weber, H. P.; Widmer, A. Molecular recognition in biological systems: models for rational drug design. Triangle 1986, 25, 131-142.
32. Taylor, P.; Mikol, V.; Kallen, J.; Burkhard, P.; Walkinshaw, M. D. Conformational polymorphism in peptidic and nonpeptidic drug molecules. Biopolymers 1997, 40, 585-592.
33. Tiberghien, F.; Kurome, T.; Takesako, K.; Didier, A.; Wenandy, T.; Loor, F. Aureobasidins: Structure-Activity Relationships for the inhibition of the human MDR1 P-glycoprotein ABC-transporter. J. Med. Chem. 2000, 43, 2547-2556.
34. Emmer, G.; Grassberger, M. A.; Schulz, G.; Boesch, D.; Gavériaux, C.; Loor, F. Derivatives of a novel cyclopeptolide. 2. Synthesis, activity against multidrug resistance in CHO and KB cells in vitro, and structure-activity relationships. J. Med. Chem. 1994, 37, 1918-1928.
35. Mikol, V.; Taylor, P.; Kallen, J.; Walkinshaw, M. D. Conformational differences of an immunosuppressant peptolide in a single crystal and in a crystal complex with human cyclophilin A. J. Mol. Biol. 1998, 283, 451-461.
36. Kessler, H.; Köck, M.; Wein, T.; Gehrke, M. 164. Reinvestigation of the conformation of cyclosporin A in chloroform. Helv. Chim. Acta 1990, 73, 1818-1832.
37. Kessler, H.; Gehrke, M.; Lautz, J.; Köck, M.; Seebach, D.; Thaler, A. Complexation and medium effects on the conformation of cyclosporin A studied by NMR spectroscopy and molecular dynamics calculations. Biochem. Pharmacol. 1990, 40, 169-173.1
38. Ko, S. Y.; Dalvit, C. Conformation of cyclosporin A in polar solvents. Int. J. Pept. Protein Res. 1992, 40, 380-382.
39. El Tayar, N.; Mark, A. E.; Vallat, P.; Brunne, R. M.; Testa, B.; van Gunsteren, W. F. Solvent-dependent conformation and hydrogen-bonding capacity of cyclosporin A: Evidence from partition coefficients and molecular dynamics simulations. J. Med. Chem. 1993, 36, 3757-3764.
40. Shaw, R. A.; Mantsch, H. H.; Chowdhry, B. Z. Solvent influence on the conformation of cyclosporin. An FT-IR study. Can. J. Chem. 1993, 71, 1334-1339.
41. Wenger, R. M.; France, J.; Bovermann, G.; Walliser, L.; Widmer, A.; Widmer, H. The 3D structure of a cyclosporin analogue in water is nearly identical to the cyclophilin-bound cyclosporin conformation. FEBS Lett. 1994, 340, 255-259.
42. O'Donohue, M. F.; Burgess, A. W.; Walkinshaw, M. D.; Treutlein, H. R. Modeling conformational changes in cyclosporin A. Protein Sci. 1995, 4, 2191-2202.
43. Janowski, B.; Fischer, G. Modulation of Cyclosporin A/Cyclophilin interactions by drug vehicles. Bioorg. Med. Chem. 1997, 5, 179-186.
44. Kallen, J.; Mikol, V.; Quesniaux, V. F. J.; Walkinshaw, M. D.; Schneider-Scherzer, E.; Schörgendorfer, K.; Weber, G.; Fliri, H. G. Cyclosporins: Recent developments in biosynthesis, pharmacology and biology, and clinical applications. In Biotechnology, 2nd edition, Vol. 7; Rehm, H. J., Reed, G., Eds.; VCH: Weinheim, 1997; Chapter 12, pp 535-591.
45. Lipinski, C. A.; Lombardo, F.; Dominy, B. W.; Feeney, P. J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Delivery Rev. 1997, 23, 3-25.
46. Quesniaux, V.; Schreier, M. H.; Wenger, R. M.; Hiestand, P. C.; Harding, M. W.; van Regenmortel, M. H. V. Cyclophilins binds to the region of cyclosporine involved in its immunosuppressive activity. Eur. J. Immunol. 1987, 17, 1359-1365.
47. Schwabe, K.; Steinheider, G.; Lawen, A.; Traber, R.; Hildebrandt, A. Reversal of multidrug resistance by novel cyclosporin A analogues and the cyclopeptolide SDZ 214-103 biosynthesized in vitro. J. Cancer Res. Clin. Oncol. 1995, 121, 407-412.
48. Tiberghien, F.; Wenandy, T.; Loor, F. The potent immunosuppressive cyclosporin FR901459 inhibits the human P-glycoprotein and formyl peptide receptor functions. J. Antibiot. 2000, 53, 509-515.
49. Foxwell, B. M. J.; Mackie, A.; Ling, V.; Ryffel, B. Identification of the multidrug resistance-related P-glycoprotein as a cyclosporine binding protein. Mol. Pharmacol. 1989, 36, 543-546.
50. Ryffel, B.; Woerly, G.; Rodriguez, C.; Foxwell, B. M. J. Identification of the multidrug resistance-related membrane glycoprotein as an acceptor for cyclosporine. J. Recept. Res. 1991, 11, 675-686.
51. Demeule, M.; Wenger, R. M.; Beliveau, R. Molecular interactions of cyclosporin A with P-glycoprotein. Photolabeling with cyclosporin derivatives. J. Biol. Chem. 1997, 272, 6647-6652.
52. Copeland, K. R.; Thliverís, J. A.; Yatscoff, R. W. Toxicity of cyclosporine metabolites. Ther. Drug Monit. 1990, 12, 525-532.
53. 2]-cyclosporin and comparison of three different X-ray data sets. Helv. Chim. Acta 1995, 78, 355-366.
54. Jette, L.; Potier, M.; Béliveau, R. P-glycoprotein is a dimer in the kidney and brain capillary membranes: effect of cyclosporin A and SDZ PSC 833. Biochemistry 1997, 36, 13929-13937.
55. Sharom, F. J.; Yu, X.; Chu, J. W. K.; Doige, C. A. Characterization of the ATPase activity of P-glycoprotein from multidrugresistant chinese hamster ovary cells. Biochem. J. 1995, 308, 381-390.
56. Demeule, M.; Jodoin, J.; Gingras, D.; Beliveau, R. P-glycoprotein is localized in caveolae in resistant cells and in brain capillaries. FEBS Lett. 2000, 466, 219-224.
57. Lucker, G. M.; Pica, C. M.; Kumar, A. S.; Covey, D. F.; PiwnicaWorms, D. Effects of cholesterol and enantiomeric cholesterol on P-glycoprotein localization and function in low-density membrane domains. Biochemistry 2000, 39, 7651-7661.
58. Loor, F.; Tiberghien, F.; Wenandy, T.; Didier, A.; Traber, R. Cyclosporins: Structure-Actitivy Relationship for the inhibition of the human FPR1 formylpeptide receptor. J. Med. Chem. 2002, 45, 4613-4628.