Structure-activity relationship and multidrug resistance study of new S-trityl-L-cysteine derivatives as inhibitors of Eg5

Journal of Medicinal Chemistry

Volumn 54, Issue 6, 2011, Pages 1576-1586

  Kaan, Hung Yi Kristal ^a   Weiss, Johanna ^b   Menger, Dominik ^b   Ulaganathan, Venkatasubramanian ^a   Tkocz, Katarzyna ^a   Laggner, Christian ^d   Popowycz, Florence ^c   Joseph, Benoît ^c   Kozielski, Frank ^a  

^a BEATSON INSTITUTE FOR CANCER RESEARCH   (United Kingdom)

^b UNIVERSITY HOSPITAL HEIDELBERG   (Germany)

^c UNIVERSITÉ LYON 1   (France)

^d UNIVERSITY OF INNSBRUCK   (Austria)

Author keywords

[No Author keywords available]

Indexed keywords

CYSTEINE DERIVATIVE; GLYCOPROTEIN P; KINESIN 5; S (2 METHYL 1,1 DIPHENYLBUTYL)CYSTEINE; S TRITYL CYSTEINE DERIVATIVE; S [1,1 DIPHENYL (4 IODOPHENYL)METHYL]CYSTEINE; S [1,1 DIPHENYL (4 THIOMETHYLPHENYL)METHYL]CYSTEINE; S [1,1 DIPHENYL (4 TRIFLUOROMETHYLPHENYL)METHYL]CYSTEINE; S [1,1 DIPHENYL [4 (ETHYL)PHENYL]METHYL]CYSTEINE; S [1,1 DIPHENYL [4 (ISOPROPYL)PHENYL]METHYL]CYSTEINE; S [1,1 DIPHENYL [4 (PROPYL)PHENYL]METHYL]CYSTEINE; UNCLASSIFIED DRUG; VINCRISTINE; ZOSUQUIDAR;

ANIMAL CELL; ARTICLE; CELL CYCLE ARREST; CELL LINE; CELL STRAIN; CONTROLLED STUDY; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TARGETING; GROWTH INHIBITION; HELA CELL; HUMAN; HUMAN CELL; IN VITRO STUDY; INHIBITION KINETICS; MITOSIS SPINDLE; MOLECULAR DOCKING; MULTIDRUG RESISTANCE; NONHUMAN; PROTEIN EXPRESSION; STRUCTURE ACTIVITY RELATION;

EID: 79952778930     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm100991m     Document Type: Article

References (42)

1. Jordan, M. A.; Wilson, L. Microtubules as a target for anticancer drugs Nature Rev. Cancer 2004, 4, 253-265 (Pubitemid 38525281)
2. Orr, G. A.; Verdier-Pinard, P.; McDaid, H.; Horwitz, S. B. Mechanisms of Taxol resistance related to microtubules Oncogene 2003, 22, 7280-7295 (Pubitemid 37487160)
3. Kavallaris, M. Microtubules and resistance to tubulin-binding agents Nature Rev. Cancer 2010, 10, 194-204
4. Kerns, E. H.; Di, L. Drug-Like Properties: Concepts, Structure Design and Methods. From ADME to Toxicity Optimization. Elsevier: New York, 2008.
5. Sarli, V.; Giannis, A. Targeting the kinesin spindle protein: basic principles and clinical implications Clin. Cancer Res. 2008, 14, 7583-7587
6. Huszar, D.; Theoclitou, M. E.; Skolnik, J.; Herbst, R. Kinesin motor proteins as targets for cancer therapy Cancer Metastasis Rev. 2009, 28, 197-208
7. Strebhardt, K.; Ullrich, A. Targeting polo-like kinase 1 for cancer therapy Nature Rev. Cancer 2006, 6, 321-330
8. Jackson, J. R.; Patrick, D. R.; Dar, M. M.; Huang, P. S. Targeted anti-mitotic therapies: can we improve on tubulin agents- Nature Rev. Cancer 2007, 7, 107-117 (Pubitemid 46160987)
9. Wood, K. W.; Chua, P.; Sutton, D.; Jackson, J. R. Centromere-associated protein E: a motor that puts the brakes on the mitotic checkpoint Clin. Cancer Res. 2008, 14, 7588-7592
10. Blangy, A.; Lane, H. A.; d'Herin, P.; Harper, M.; Kress, M.; Nigg, E. A. Phosphorylation by p34cdc2 regulates spindle association of human Eg5, a kinesin-related motor essential for bipolar spindle formation in vivo Cell 1995, 83, 1159-1169
11. Rowinsky, E. K.; Eisenhauer, E. A.; Chaudhry, V.; Arbuck, S. G.; Donehower, R. C. Clinical toxicities encountered with paclitaxel (Taxol) Semin. Oncol. 1993, 20, 1-15 (Pubitemid 23239390)
12. DeBonis, S.; Skoufias, D. A.; Lebeau, L.; Lopez, R.; Robin, G.; Margolis, R. L.; Wade, R. H.; Kozielski, F. In vitro screening for inhibitors of the human mitotic kinesin Eg5 with antimitotic and antitumor activities Mol. Cancer Ther. 2004, 3, 1079-1090 (Pubitemid 39295005)
13. Kozielski, F.; DeBonis, S.; Skoufias, D. A. Screening for inhibitors of microtubule-associated motor proteins Methods Mol. Med. 2007, 137, 189-207
14. Skoufias, D. A.; DeBonis, S.; Saoudi, Y.; Lebeau, L.; Crevel, I.; Cross, R.; Wade, R. H.; Hackney, D.; Kozielski, F. S -Trityl- l -cysteine is a reversible, tight binding inhibitor of the human kinesin Eg5 that specifically blocks mitotic progression J. Biol. Chem. 2006, 281, 17559-17569 (Pubitemid 44035555)
15. Kozielski, F.; Skoufias, D. A.; Indorato, R. L.; Saoudi, Y.; Jungblut, P. R.; Hustoft, H. K.; Strozynski, M.; Thiede, B. Proteome analysis of apoptosis signaling by S -trityl- l -cysteine, a potent reversible inhibitor of human mitotic kinesin Eg5 Proteomics 2008, 8, 289-300 (Pubitemid 351212328)
16. Ogo, N.; Oishi, S.; Matsuno, K.; Sawada, J.; Fujii, N.; Asai, A. Synthesis and biological evaluation of l -cysteine derivatives as mitotic kinesin Eg5 inhibitors Bioorg. Med. Chem. Lett. 2007, 17, 3921-3924 (Pubitemid 46920939)
17. Debonis, S.; Skoufias, D. A.; Indorato, R. L.; Liger, F.; Marquet, B.; Laggner, C.; Joseph, B.; Kozielski, F. Structure-activity relationship of S -trityl- l -cysteine analogues as inhibitors of the human mitotic kinesin Eg5 J. Med. Chem. 2008, 51, 1115-1125 (Pubitemid 351480375)
18. Zee-Cheng, K. Y.; Cheng, C. C. Experimental antileukemic agents. Preparation and structure-activity study of S -tritylcysteine and related compounds J. Med. Chem. 1970, 13, 414-418
19. Konig, W.; Geiger, R.; Siedel, W. New S-protecting groups for cystein Chem. Ber. 1968, 101, 681-693
20. Marvel, C. S.; Dietz, F. C.; Himel, C. M. The dissociation of hexaarylethanes. XIII. Halogen substituents J. Org. Chem. 1942, 7, 392-396
21. Murphy, D. J. Determination of accurate KI values for tight-binding enzyme inhibitors: an in silico study of experimental error and assay design Anal. Biochem. 2004, 327, 61-67 (Pubitemid 38367983)
22. Kaan, H. Y.; Ulaganathan, V.; Hackney, D. D.; Kozielski, F. An allosteric transition trapped in an intermediate state of a new kinesin-inhibitor complex Biochem. J. 2010, 425, 55-60
23. Wiltshire, C.; Singh, B. L.; Stockley, J.; Fleming, J.; Doyle, B.; Barnetson, R.; Robson, C. N.; Kozielski, F.; Leung, H. Y. Docetaxel-resistant prostate cancer cells remain sensitive to S -trityl- l -cysteine-mediated Eg5 inhibition Mol. Cancer Ther. 2010, 9, 1730-1739
24. Sakowicz, R.; Finer, J. T.; Beraud, C.; Crompton, A.; Lewis, E.; Fritsch, A.; Lee, Y.; Mak, J.; Moody, R.; Turincio, R.; Chabala, J. C.; Gonzales, P.; Roth, S.; Weitman, S.; Wood, K. W. Antitumor activity of a kinesin inhibitor Cancer Res. 2004, 64, 3276-3280 (Pubitemid 38581433)
25. Marcus, A. I.; Peters, U.; Thomas, S. L.; Garrett, S.; Zelnak, A.; Kapoor, T. M.; Giannakakou, P. Mitotic kinesin inhibitors induce mitotic arrest and cell death in Taxol-resistant and -sensitive cancer cells J. Biol. Chem. 2005, 280, 11569-11577 (Pubitemid 40418469)
26. Peters, T.; Lindenmaier, H.; Haefeli, W. E.; Weiss, J. Interaction of the mitotic kinesin Eg5 inhibitor monastrol with P-glycoprotein Naunyn Schmiedeberg's Arch. Pharmacol. 2006, 372, 291-299 (Pubitemid 43119563)
27. Cox, C. D.; Breslin, M. J.; Whitman, D. B.; Coleman, P. J.; Garbaccio, R. M.; Fraley, M. E.; Zrada, M. M.; Buser, C. A.; Walsh, E. S.; Hamilton, K.; Lobell, R. B.; Tao, W.; Abrams, M. T.; South, V. J.; Huber, H. E.; Kohl, N. E.; Hartman, G. D. Kinesin spindle protein (KSP) inhibitors. Part V: discovery of 2-propylamino-2,4-diaryl-2,5-dihydropyrroles as potent, water-soluble KSP inhibitors, and modulation of their basicity by beta-fluorination to overcome cellular efflux by P-glycoprotein Bioorg. Med. Chem. Lett. 2007, 17, 2697-2702 (Pubitemid 46636272)
28. Cox, C. D.; Coleman, P. J.; Breslin, M. J.; Whitman, D. B.; Garbaccio, R. M.; Fraley, M. E.; Buser, C. A.; Walsh, E. S.; Hamilton, K.; Schaber, M. D.; Lobell, R. B.; Tao, W.; Davide, J. P.; Diehl, R. E.; Abrams, M. T.; South, V. J.; Huber, H. E.; Torrent, M.; Prueksaritanont, T.; Li, C.; Slaughter, D. E.; Mahan, E.; Fernandez-Metzler, C.; Yan, Y.; Kuo, L. C.; Kohl, N. E.; Hartman, G. D. Kinesin spindle protein (KSP) inhibitors. 9. Discovery of (2 S)-4-(2,5-difluorophenyl)- n -[(3 R,4 S)-3-fluoro-1-methylpiperidin-4-yl]-2- (hydroxymethyl)- N -methyl-2-phenyl-2,5-dihydro-1 H -pyrrole-1-carboxamide (MK-0731) for the treatment of taxane-refractory cancer J. Med. Chem. 2008, 51, 4239-4352
29. Gold Suite 1.0.1; Cambridge Crystallographic Data Centre: Cambridge, UK, 2008.
30. Kim, E. D.; Buckley, R.; Learman, S.; Richard, J.; Parke, C.; Worthylake, D. K.; Wojcik, E. J.; Walker, R. A.; Kim, S. Allosteric drug discrimination is coupled to mechanochemical changes in the kinesin-5 motor core J. Biol. Chem. 2010, 285, 18650-18661
31. Zee-Cheng, K. Y.; Cheng, C. C. Structural modification of S -trityl- l -cysteine. Preparation of some S -(substituted trityl)- l -cysteines and dipeptides of S -trityl- l -cysteine J. Med. Chem. 1972, 15, 13-16
32. Kessel, D.; Smith, G.; Blahnik, J. Effects of S -(trityl)- l -cysteine and its analogs on cell surface properties of leukemia L1210 cells Biochem. Pharmacol. 1976, 25, 1893-1897
33. Paull, K. D.; Lin, C. M.; Malspeis, L.; Hamel, E. Identification of novel antimitotic agents acting at the tubulin level by computer-assisted evaluation of differential cytotoxicity data Cancer Res. 1992, 52, 3892-3900
34. Brier, S.; Lemaire, D.; DeBonis, S.; Forest, E.; Kozielski, F. Molecular dissection of the inhibitor binding pocket of mitotic kinesin Eg5 reveals mutants that confer resistance to antimitotic agents J. Mol. Biol. 2006, 360, 360-376 (Pubitemid 43927825)
35. Brier, S.; Lemaire, D.; Debonis, S.; Forest, E.; Kozielski, F. Identification of the protein binding region of S -trityl- l -cysteine, a new potent inhibitor of the mitotic kinesin Eg5 Biochemistry 2004, 43, 13072-13082 (Pubitemid 39362777)
36. Brier, S.; Lemaire, D.; DeBonis, S.; Kozielski, F.; Forest, E. Use of hydrogen/deuterium exchange mass spectrometry and mutagenesis as a tool to identify the binding region of inhibitors targeting the human mitotic kinesin Eg5 Rapid Commun. Mass Spectrom. 2006, 20, 456-462 (Pubitemid 43200370)
37. Copeland, R. A. Tight binding inhibition. In Evaluation of Enzyme Inhibitors in Drug Discovery; John Wiley & Sons: New York, 2005; pp 178 - 213.
38. Weiss, J.; Herzog, M.; Konig, S.; Storch, C. H.; Ketabi-Kiyanvash, N.; Haefeli, W. E. Induction of multiple drug transporters by efavirenz J. Pharmacol. Sci. 2009, 109, 242-250
39. Weiss, J.; Dormann, S. M.; Martin-Facklam, M.; Kerpen, C. J.; Ketabi-Kiyanvash, N.; Haefeli, W. E. Inhibition of P-glycoprotein by newer antidepressants J. Pharmacol. Exp. Ther. 2003, 305, 197-204 (Pubitemid 36373851)
40. Omega 2.2.1, OpenEye Scientific Software: Santa Fe, NM, USA, 2007.
41. LigandScout 2.03; Inte:Ligand GmbH: Vienna, 2009.
42. Cruickshank, D. W. Remarks about protein structure precision Acta Crystallogr., Sect. D: Biol. Crystallogr. 1999, 55, 583-601 (Pubitemid 29139232)