Total synthesis and biological assessment of benzimidazole-based analogues of epothilone A: Ambivalent effects on cancer cell growth inhibition

ChemBioChem

Volumn 7, Issue 1, 2006, Pages 54-57

  Cachoux, Fréderic ^b   Isarno, Thomas ^c   Wartmann, Markus ^d   Altmann, Karl Heinz ^a  

^a ETH ZURICH   (Switzerland)

^b Prestwick Chemical Inc   (France)

^c Carbogen AG   (Switzerland)

^d NOVARTIS PHARMA AG   (Switzerland)

Author keywords

Antitumor agents; Drug discovery; Epothilones; Microtubule stabilizer; Natural products; Total synthesis

Indexed keywords

ANTINEOPLASTIC AGENT; BENZIMIDAZOLE DERIVATIVE; EPOTHILONE A; GLYCOPROTEIN P; NATURAL PRODUCT; THIAZOLE DERIVATIVE; TUBULIN;

ARTICLE; CANCER CELL CULTURE; CANCER INHIBITION; CELL PROLIFERATION; CONTROLLED STUDY; DRUG POTENCY; DRUG SYNTHESIS; EPOXIDATION; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN CELL; MICROTUBULE ASSEMBLY; PRIORITY JOURNAL; STEREOCHEMISTRY; SUZUKI REACTION;

BENZIMIDAZOLES; CELL LINE, TUMOR; CELL PROLIFERATION; DRUG SCREENING ASSAYS, ANTITUMOR; EPOTHILONES; HUMANS; MOLECULAR CONFORMATION; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 30444438771     PISSN: 14394227     EISSN: None     Source Type: Journal    
DOI: 10.1002/cbic.200500351     Document Type: Article

References (35)

1. For recent reviews see, for example, a) K.-H. Altmann, Curr. Opin. Chem. Biol. 2001, 5, 424-431;
2. b) D. C. Myles, Annu. Rep. Med. Chem. 2002, 37, 125-132.
3. E. K. Rowinsky, Annu. Rev. Med. 1997, 48, 353-374.
4. a) G. Höfle, N. Bedorf, K. Gerth, H. Reichenbach, German patent disclosure DE 4138042, May 5, 1993 (Priority Nov. 19, 1991);
5. b) K. Gerth, N. Bedorf, G. Höfle, H. Irschik, H. Reichenbach, J. Antibiot. 1996, 49, 560-564.
6. For reviews see, for example, a) K.-H. Altmann, Curr. Pharm. Des. 2005, 11, 1595-1613;
7. b) K.-H. Altmann, Org. Biomol. Chem. 2004, 2137-2152;
8. c) A. Rivkin, T.-C. Chou, S. J. Danishefsky, Angew. Chem. 2005, 117, 2898-2910;
9. Angew. Chem. Int. Ed. 2005, 44, 2838-2850;
10. d) R. M. Borzilleri, G. D. Vite, Drugs Future 2002, 27, 1149-1163;
11. e) C. R. Harris, S. J. Danishefsky, J. Org. Chem. 1999, 64, 8434-8456;
12. f) K. C. Nicolaou, F. Roschangar, D. Vourloumis, Angew. Chem. 1998, 110, 2120-2153;
13. Angew. Chem. Int. Ed. 1998, 37, 2014-2045.
14. F. Cachoux, T. Isarno, M. Wartmann, K.-H. Altmann, Angew. Chem. 2005, 117, 7636-7640;
15. Angew. Chem. Int. Ed. 2005, 44, 7469-7473.
16. K.-H. Altmann, G. Bold, G. Caravatti, A. Flörsheimer, V. Guagnano, M. Wartmann, Bioorg. Med. Chem. Lett. 2000, 10, 2765-2768.
17. Epo C and D are 12/13-deoxy derivatives of Epo A and B, respectively, that is, they incorporate a as double bond between C12 and C13 in place of an epoxide moiety.
18. a) K.-H. Altmann, G. Bold, G. Caravatti, D. Denni, A. Flörsheimer, A. Schmidt, G. Rihs, M. Wartmann, Helv. Chim. Acta 2002, 85, 4086-4110;
19. b) K. C. Nicolaou, N. Winssinger, J. Pastor, S. Ninkovic, F. Sarabia, Y. He, D. Vourloumis, Z. Yang, T. Li, P. Giannakakou, E. Hamel, Nature 1997, 387, 268-272.
20. R. S. Chemler, D. Trauner, S. J. Danishefsky, Angew. Chem. 2001, 113, 4676-4701;
21. Angew. Chem. Int. Ed. 2001, 40, 4544-4568.
22. G. Stork, K. Zhao, Tetrahedron Lett. 1989, 30, 2173-2174.
23. J. Inanaga, K. Hirata, H. Saeki, T. Katsuki, M. Yamaguchi, Bull. Chem. Soc. Jpn. 1979, 52, 1989-1993.
24. J. Rudolph, K. L. Reddy, J. P. Chang, K. B. Sharpless, J. Am. Chem. Soc. 1997, 119, 6189-6190.
25. a) K. Takai, K. Nitta, K. Utimoto, J. Am. Chem. Soc. 1986, 108, 7408-7410;
26. b) K. Takai, T. Ichiguchi, S. Hikasa, Synlett 1999, 8, 1268-1270;
27. c) D. A. Evans, W. C. Black, J. Am. Chem. Soc. 1993, 115, 1197-4513.
28. Z.-X. Wang, Y. Tu, M. Frohn, J.-R. Zhang, Y. Shi, J. Am. Chem. Soc. 1997, 119, 11224-11235.
29. These activity differences should not be taken to indicate that the antiproliferative effects of analogues 2 and 3 would (additionally) be mediated through interactions with target proteins other than tubulin (given the fact that all new analogues appear to be essentially equipotent inducers of tubulin polymerization). Apart from interaction with a target protein, cellular activity is also modulated by other factors, such as cellular uptake, intracellular distribution or metabolic stability. For example, the differences in cellular potency between Epo B and D are caused, at least in part, by differences in uptake efficiency: R. B. Lichtner, A. Rotgeri, T. Bunte, B. Buchmann, J. Hoffmann, W. Schwede, W. Skuballa, U. Klar, Proc. Natl. Acad. Sci. USA 2001, 98, 11 743-11 748.
30. M. Wartmann, K.-H. Altmann, Curr. Med. Chem: Anti-Cancer Agents 2002, 2, 123-148.
31. To put the activity of compound 3 in perspective, it should be noted that, with one exception, all publicly known compounds of the epothilone class in clinical development are less potent than Epo B.
32. [16] and BMS-310705 (10-fold; M. Wartmann, unpublished results).
33. C. M. Lin, Y. Q. Jiang, A. G. Chaudhary, J. M. Rimoldi, D. G. Kingston, E. Hamel, Cancer Chemother. Pharmacol. 1996, 38, 136-140.
34. a) T. Meyer, U. Regenass, D. Fabbro, E. Alteri, J. Rösel, M. Müller, G. Caravatti, A. Matter, Int. J. Cancer 1989, 43, 851-856;
35. b) K. C. Nicolaou, R. Scarpelli, B. Bollbuck, B. Werschkun, M. M. Pereira, M. Wartmann, K.-H. Altmann, D. Zaharevitz, R. Gussio, P. Giannakakou, Chem. Biol. 2000, 7, 593-599.