Lead identification of conformationally restricted benzoxepin type combretastatin analogs: Synthesis, antiproliferative activity, and tubulin effects

Journal of Enzyme Inhibition and Medicinal Chemistry

Volumn 25, Issue 2, 2010, Pages 180-194

  Barrett, Irene ^a   Carr, Miriam ^a   O'Boyle, Niamh ^a   Greene, Lisa M ^a   J S Knox, Andrew ^a   Lloyd, David G ^a   Zisterer, Daniela M ^a   Meegan, Mary J ^a  

^a TRINITY COLLEGE DUBLIN   (Ireland)

Author keywords

Antiproliferative activity; Benzoxepin; Combretastatin analogs

Indexed keywords

3,4 DIHYDRO 2H 1 BENZOXEPIN 5 ONE; 4 (3,4 DIMETHOXY PHENOXY) BUTYRIC ACID; 4 (3,5 DIMETHOXY PHENOXY) BUTYRIC ACID; 4 BROMO 5 (3 FLUORO 4 METHOXYPHENYL) 2,3 DIHYDRO 1 BENZOXEPIN; 4 BROMO 5 (3 FORMYL 4 METHOXYPHENYL) 2,3 DIHYDRO 1 BENZOXEPIN; 4 BROMO 5 (3,4 DIMETHOXYPHENYL) 2,3 DIHYDRO 1 BENZOXEPIN; 4 BROMO 5 (3,4,5 TRIMETHOXYPHENYL) 2,3 DIHYDRO 1 BENZOXEPIN; 4 BROMO 5 (4 HYDROXYPHENYL) 2,3 DIHYDRO 1 BENZOXEPIN; 4 BROMO 5 (4 METHOXYPHENYL) 2,3 DIHYDRO 1 BENZOXEPIN; 4 BROMO 7,8 DIMETHOXY 5 (4 METHOXY PHENYL) 2,3 DIHYDRO BENZO[B]OXEPIN; 5 (3 FLUORO 4 METHOXYPHENYL) 2,3 DIHYDRO 1 BENZOXEPIN; 5 (3 FORMYL 4 METHOXYPHENYL) 2,3 DIHYDRO 1 BENZOXEPIN; 5 (3 HYDROXY 4 METHOXYPHENYL) 4 (3,4,5 TRIMETHOXYPHENYL) 2,3 DIHYDRO BENZOXEPINE; 5 (3,4 DIMETHOXYPHENYL) 2,3 DIHYDRO 1 BENZOXEPIN; 5 (3,4 DIMETHOXYPHENYL) 4 (2,3,4 TRIMETHOXYPHENYL) 2,3 DIHYDRO BENZOXEPIN; 5 (3,4 DIMETHOXYPHENYL) 4 (3,4,5 TRIMETHOXYPHENYL) 2, 3 DIHYDRO 1 BENZOXEPIN; 5 (3,4,5 TRIMETHOXYPHENYL) 2,3 DIHYDRO 1 BENZOXEPIN; 5 (4 HYDROXY PHENYL) 2,3 DIHYDRO 1 BENZOXEPIN; 5 (4 METHOXYPHENYL) 2,3 DIHYDRO 1 BENZOXEPIN; 5 (4 METHOXYPHENYL) 4 (3,4,5 TRIMETHOXYPHENYL) 2,3 DIHYDRO 1 BENZOXEPIN; 6,7 DIMETHOXY 3,4 DIHYDRO 2H BENZO[B]OXEPIN 5 ONE; 6,8 DIMETHOXY 3,4 DIHYDRO 2H BENZO[B]OXEPIN 5 ONE; 6,8 DIMETHOXY 4 BROMO 5 (4 METHOXYPHENYL) 2,3 DIHYDROBENZOXEPIN; 6,8 DIMETHOXY 5 (4 METHOXYPHENYL) 2,3 DIHYDROBENZOXEPIN; 7,8 DIMETHOXY 5 (4 METHOXY PHENYL) 2,3 DIHYDROBENZO[B]OXEPIN; ANTINEOPLASTIC AGENT; BENZOXEPIN DERIVATIVE; COMBRETASTATIN A4; TUBULIN; UNCLASSIFIED DRUG; UNINDEXED DRUG;

BREAST CANCER; CANCER CELL CULTURE; CELL STRAIN MCF 7; CONFERENCE PAPER; CONFORMATION; CONTROLLED STUDY; DRUG ACTIVITY; DRUG IDENTIFICATION; HUMAN; HUMAN CELL; PRIORITY JOURNAL; QUANTITATIVE STRUCTURE ACTIVITY RELATION;

ANTINEOPLASTIC AGENTS, PHYTOGENIC; BENZOXEPINS; BINDING SITES; BREAST NEOPLASMS; CELL LINE, TUMOR; CELL PROLIFERATION; DRUG DESIGN; FEMALE; HUMANS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PROTEIN BINDING; STILBENES; STRUCTURE-ACTIVITY RELATIONSHIP; TUBULIN;

EID: 77949437448     PISSN: 14756366     EISSN: 14756374     Source Type: Journal    
DOI: 10.3109/14756360903169659     Document Type: Conference Paper

References (36)

1. Jordan MA, Wilson L.Microtubules as a target for anticancer drugs.Nat Rev Cancer 2004, 4: 253-265
2. Jordan MA. Mechanism of action of antitumor drugs that interact with microtubules and tubulin. Curr Med Chem Anticancer Agents 2002;2:1-17.
3. Attard G, Greystoke A, Kaye S, De Bono J. Update on tubulin-binding agents. Pathol Biol (Paris) 2006;54:72-84.
4. Tron GC, Pagliai F, Del Grosso E, Genazzani AA, Sorba G. Synthesis and cytotoxic evaluation of combretafurazans. J Med Chem 2005;48:3260-3268
5. ter Haar E, Rosenkranz HS, Hamel E, Day BW. Computational and molecular modeling evaluation of the structural basis for tubulin polymerization inhibition by colchicine site agents. Bioorg Med Chem 1996;4:1659-1671
6. Rai SS, Wolff J. Localization of the vinblastine-binding site on betatubulin. J Biol Chem 1996;271:14707-14711
7. Pettit GR, Singh SB, Boyd MR, Hamel E, Pettit RK, Schmidt JM, et al. Antineoplastic agents. 291.Isolation and synthesis of combretastatins A-4, A-5, and A-6(1a). J Med Chem 1995;38:1666-1672
8. Andreu JM, Barasoain I. The interaction of baccatin III with the taxol binding site of microtubules determined by a homogeneous assay with fluorescent taxoid. Biochemistry 2001;40:11975-11984
9. Diaz JF, Barasoain I, Andreu JM. Fast kinetics of Taxol binding to microtubules. Effects of solution variables and microtubule-associated proteins. J Biol Chem 2003;278:8407-8419
10. Pettit GR, Rhodes MR, Herald DL, Hamel E, Schmidt JM, Pettit RK. Antineoplastic agents. 445. Synthesis and evaluation of structural modifications of (Z)- and (E)-combretastatin A-41. J Med Chem 2005;48:4087-4099
11. Pettit GR, Singh SB, Hamel E, Lin CM, Alberts DS, Garcia-Kendall D. Isolation and structure of the strong cell growth and tubulin inhibitor combretastatin A-4. Experientia 1989;45:209-211
12. Hori K. Antineoplastic strategy: irreversible tumor blood flow stasis induced by the combretastatin A-4 derivative AVE8062 (AC7700). Chemotherapy 2005;51:357-360
13. Nam NH. Combretastatin A-4 analogues as antimitotic antitumor agents. Curr Med Chem 2003;10:1697-1722
14. Bailly C, Bal C, Barbier P, Combes S, Finet JP, Hildebrand MP, et al. Synthesis and biological evaluation of 4-arylcoumarin analogues of combretastatins. J Med Chem 2003;46:5437-5444
15. Ganina OG, Daras E, Bourgarel-Rey V, Peyrot V, Andresyuk AN, Finet JP, et al. Synthesis and biological evaluation of polymethoxylated 4-heteroarylcoumarins as tubulin assembly inhibitor. Bioorg Med Chem 2008;16:8806-8812
16. Kim Y, Nam NH, You YJ, Ahn BZ. Synthesis and cytotoxicity of 3,4-diaryl- 2(5H)-furanones. Bioorg Med Chem Lett 2002;12:719-722
17. Wang L, Woods KW, Li Q, Barr KJ, McCroskey RW, Hannick SM, et al. Potent, orally active heterocycle-based combretastatin A-4 analogues: synthesis, structure-activity relationship, pharmacokinetics, and in vivo antitumor activity evaluation. J Med Chem 2002;45:1697-1711
18. Pirali T, Busacca S, Beltrami L, Imovilli D, Pagliai F, Miglio G, et al. Synthesis and cytotoxic evaluation of combretafurans, potential scaffolds for dual-action antitumoral agents. J Med Chem 2006; 49:5372-5376
19. Medarde M, Ramos A, Caballero E, De Clairac RPL, Lopez JL, Gravalos DG, et al. Synthesis and antineoplastic activity of combretastatin analogues: heterocombretastatins. Eur J Med Chem 1998;33:71-77
20. De Martino G, La Regina G, Coluccia A, Edler MC, Barbera MC, Brancale A, et al. Arylthioindoles, potent inhibitors of tubulin polymerization. J Med Chem 2004;47:6120-6123
21. Lloyd DG, Hughes RB, Zisterer DM, Williams DC, Fattorusso C, Catalanotti B, et al. Benzoxepin-derived estrogen receptor modulators: a novel molecular scaffold for the estrogen receptor. J Med Chem 2004;47:5612-5615
22. Meegan MJ, Barrett I, Zimmermann J, Knox AJ, Zisterer DM, Lloyd DG. Benzothiepin-derived molecular scaffolds for estrogen receptor modulators: synthesis and antagonistic effects in breast cancer cells. J Enzyme Inhib Med Chem 2007;22:655-666
23. Cushman M, Nagarathnam D, Gopal D, Chakraborti AK, Lin CM, Hamel E. Synthesis and evaluation of stilbene and dihydrostilbene derivatives as potential anticancer agents that inhibit tubulin polymerization. J Med Chem 1991;34:2579-2588
24. Freedman JS, Kenneth T. The preparation of 3,4-dihydro-1-benzoxepin- 5(2H)-ones. J Heterocycl Chem 1989;26:1547-1554
25. Tandon VK, Khanna JM, Arand N, Srimal RC, Prasad CR. Agents acting on the central nervous system. XX.5-Subsitituted and 4,5-disubstituted 2,3,4,5-tetrahydro-1-benzoxepines. Indian J Chem 1975;13:1-8.
26. ACD/Chemsketch v10. Atlanta, GA: Advanced Chemistry Labs (http:// www.acdlabs.com/download/chemsk.html).
27. Molecular Operating Environment (MOE). Montreal: Chemical Computing Group (http://www.chemcomp.com).
28. Zhang SX, Feng J, Kuo SC, Brossi A, Hamel E, Tropsha A, et al.Antitumor agents. 199. Three-dimensional quantitative structure-activity relationship study of the colchicine binding site ligands using comparative molecular field analysis. J Med Chem 2000;43:167-176
29. Boland GM, Donnelly DMX, Finet JP, Rea MD. Synthesis of neoflavones by Suzuki arylation of 4-substituted coumarins. J Chem Soc Perkin Trans 1 1996;(21):2591-2597
30. Flynn BL, Flynn GP, Hamel E, Jung MK. The synthesis and tubulin binding activity of thiophene-based analogues of combretastatin A-4. Bioorg Med Chem Lett 2001;11:2341-2343
31. Gaukroger K, Hadfield JA, Lawrence NJ, Nolan S, McGown AT. Structural requirements for the interaction of combretastatins with tubulin: how important is the trimethoxy unit? Org Biomol Chem 2003;1:3033-3037
32. Lawrence NJ, Hepworth LA, Rennison D, McGown AT, Hadfield JA. Synthesis and anticancer activity of fluorinated analogues of combretastatin A-4. J Fluorine Chem 2003;123:101-108
33. Maya AB, Del Rey B, Lamamie de Clairac RP, Caballero E, Barasoain I, Andreu JM, et al. Design, synthesis and cytotoxic activities of naphthyl analogues of combretastatin A-4. Bioorg Med Chem Lett 2000;10:2549-2551
34. Ravelli RB, Gigant B, Curmi PA, Jourdain I, Lachkar S, Sobel A, et al. Insight into tubulin regulation from a complex with colchicine and a stathmin-like domain. Nature 2004;428:198-202.
35. Jordan A, Hadfield JA, Lawrence NJ, McGown AT. Tubulin as a target for anticancer drugs: agents which interact with the mitotic spindle. Med Res Rev 1998;18:259-296
36. Springer C, Adalsteinsson H, Young MM, Kegelmeyer PW, Roe DC. PostDOCK: a structural, empirical approach to scoring protein ligand complexes. J Med Chem 2005;48:6821-6831