Synthesis and biological properties of benzothiazole, benzoxazole, and chromen-4-one analogues of the potent antitumor agent 2-(3,4-dimethoxyphenyl)-5- fluorobenzothiazole (PMX 610, NSC 721648)

Journal of Medicinal Chemistry

Volumn 51, Issue 16, 2008, Pages 5135-5139

  Aiello, Stefania ^a,b   Wells, Geoffrey ^c,d   Stone, Erica L ^e   Kadri, Hachemi ^a   Bazzi, Rana ^e   Bell, David R ^e   Stevens, Malcolm F G ^c,e   Matthews, Charles S ^e   Bradshaw, Tracey D ^e   Westwell, Andrew D ^a  

^a CARDIFF UNIVERSITY   (United Kingdom)

^b UNIVERSITY OF PALERMO   (Italy)

^c Pharminox Ltd   (United Kingdom)

^d UNIVERSITY OF LONDON   (United Kingdom)

^e UNIVERSITY OF NOTTINGHAM   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

2 (3,4 DIMETHOXYPHENYL) 5 FLUOROBENZOTHIAZOLE; ANTINEOPLASTIC AGENT; BENZOTHIAZOLE DERIVATIVE; BENZOXAZOLE DERIVATIVE; CHROMEN 4 ONE DERIVATIVE; NSC 721648; PMX 610; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; ARTICLE; BIOLOGICAL ACTIVITY; BREAST CANCER; CANCER CELL CULTURE; CANCER INHIBITION; CONTROLLED STUDY; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; HUMAN; HUMAN CELL;

ANTINEOPLASTIC AGENTS; BENZOPYRANS; BENZOTHIAZOLES; BENZOXAZOLES; BREAST NEOPLASMS; CELL CYCLE; CELL LINE, TUMOR; HUMANS; RECEPTORS, ARYL HYDROCARBON; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 50249175183     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm800418z     Document Type: Article

References (24)

1. This paper is part 29 in the series on antitumor benzothiazoles. Part 28: Bradshaw, T. D.; Stone, E.; Trapani, V.; Leong, C.-E.; Matthews, C. S.; te Poele, R.; Stevens, M. F. G. Mechanisms of acquired resistance to 2-(4-amino-3-methylphenyl)benzothiazole in breast cancer cell lines. Breast Cancer Res. Treat. 2008, 110, 57-68.
2. Bradshaw, T. D.; Westwell, A. D. The development of the antitumour benzothiazole prodrug, phortress, as a clinical candidate. Curr. Med. Chem. 2004, 11, 1241-1253.
3. Westwell, A. D.; Stevens, M. F. G. Hitting the chemotherapy jackpot: strategy, productivity and chemistry. Drug Discovery Today 2004, 9, 625-627.
4. Shi, D.-F.; Bradshaw, T. D.; Wrigley, S.; McCall, C. J.; Lelieveld, P.; Fichtner, I.; Stevens, M. F. G. Antitumor benzothiazoles. 3. Synthesis of 2-(4-aminophenyl)benzothiazoles and evaluation of their activities against breast cancer cell lines in vitro and in vivo. J. Med. Chem. 1996, 39, 3375-3384.
5. Loaiza-Pérez, A. L.; Trapani, V.; Hose, C.; Singh, S. S.; Trepel, J.; Stevens, M. F. G.; Bradshaw, T. D.; Sausville, E. A. The aryl hydrocarbon receptor mediates sensitivity of MCF-7 breast cancer cells to the antitumor agent 2-(4-amino-3-methylphenyl)benzothiazole. Mol. Pharmacol. 2002, 61, 13-19.
6. Trapani, V.; Patel, V.; Ciolino, H. P.; Yen, G. C.; Hose, C.; Trepel, J. B.; Stevens, M. F. G.; Sausville, E. A.; Loaiza-Pérez, A. L. DNA damage and cell cycle arrest induced by 2-(4-amino-3-methylphenyl)-5- fluorobenzothiazole (5F 203, NSC 703786) is attenuated in aryl hydrocarbon receptor deficient MCF-7 cells. Br. J. Cancer 2003, 88, 599-605.
7. Chua, M.-S.; Kashiyama, E.; Bradshaw, T. D.; Stinson, S. F.; Brantley, E.; Sausville, E. A.; Stevens, M. F. G. Role of CYP1A1 in modulation of antitumor properties of the novel agent 2-(4-amino-3-methylphenyl)benzothiazole (DF 203, NSC 674495) in human breast cancer cells. Cancer Res. 2000, 60, 5196-5203.
8. Brantley, E.; Trapani, V.; Alley, M. C.; Hose, C. D.; Bradshaw, T. D.; Stevens, M. F. G.; Sausville, E. A.; Stinson, S. F. Fluorinated 2-(4-amino-3-methylphenyl)benzothiazoles induce CYP1A1 expression, become metabolized, and bind to macromolecules in sensitive human cancer cells. Drug Metab. Dispos. 2004, 32, 1392-1401.
9. Kashiyama, E.; Hutchinson, I.; Chua, M-S.; Stinson, S. F.; Phillips, L. R.; Kaur, G.; Sausville, E. A.; Bradshaw, T. D.; Westwell, A. D.; Stevens, M. F. G. Antitumor benzothiazoles. 8. Synthesis, metabolic formation, and biological properties of the C- and N-oxidation products of antitumor 2-(4-aminophenyl) benzothiazoles. J. Med. Chem. 1999, 42, 4172-4184.
10. Hutchinson, I.; Chua, M-Z.; Browne, H. L.; Trapani, V.; Bradshaw, T. D.; Westwell, A. D.; Stevens, M. F. G. Antitumor benzothiazoles. 14. Synthesis and in vitro biological properties of fluorinated 2-(4-aminophenyl)benzothiazoles. J. Med. Chem. 2001, 44, 1445-1455.
11. Leong, C. O.; Suggitt, M.; Swaine, D. J.; Bibby, M. C.; Stevens, M. F. G.; Bradshaw, T. D. In vitro, in vivo, and in silico analyses of the antitumor activity of 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazoles. Mol. Cancer Ther. 2004, 3, 1565-1575.
12. Fichtner, I.; Monks, A.; Hose, C.; Stevens, M. F. G.; Bradshaw, T. D. The experimental antitumor agents phortress and doxorubicin are equiactive against human-derived breast carcinoma xenograft models. Breast Cancer Res. Treat. 2004, 87, 97-107.
13. Hutchinson, I.; Jennings, S. A.; Vishnuvajjala, B. R.; Westwell, A. D.; Stevens, M. F. G. Antitumor benzothiazoles. 16. Synthesis and pharmaceutical properties of antitumor 2-(4-aminophenyl)benzothiazole amino acid prodrugs. J. Med. Chem. 2002, 45, 744-747.
14. 11C-labeled 6-substituted 2-arylbenzothiazoles as amyloid imaging agents. J. Med. Chem. 2003, 46, 2740-2754.
15. Price, J. C.; Klunk, W. E.; Lopresti, B. J.; Lu, X.; Hoge, J. A.; Ziolko, S. K.; Holt, D. P.; Meltzer, C. C.; DeKosty, S. T.; Mathis, C. A. Kinetic modelling of amyloid binding in humans using PET imaging and Pittsburgh compound-B. J. Cereb. Blood Flow Metab. 2005, 25, 1528-1547.
16. Henriksen, G.; Hauser, A. I.; Westwell, A. D.; Yousefi, B. H.; Schwaiger, M.; Drzezga, A.; Wester, H.-J. Metabolically stabilized benzothiazoles for imaging of amyloid plaques. J. Med. Chem. 2007, 50, 1087-1089.
17. Mortimer, C. G.; Wells, G.; Crochard, J.-P.; Stone, E. L.; Bradshaw, T. D.; Stevens, M. F. G.; Westwell, A. D. Antitumor benzothiazoles. 26. 2-(3,4-Dimethoxyphenyl)-5-fluorobenzothiazole (GW 610, NSC 721648), a simple fluorinated 2-arylbenzothiazole, shows potent and selective inhibitory activity against lung, colon, and breast cancer cell lines. J. Med. Chem. 2006, 49, 179-185.
18. Stevens, M. F. G.; McCall, C. J.; Lelieveld, P.; Alexander, P.; Richter, A.; Davies, D. E. Structural studies on bioactive compounds. 23. Synthesis of polyhydroxylated 2-phenylbenzothiazoles and a comparison of their cytotoxicities and pharmacological properties with genistein and quercetin. J. Med. Chem. 1994, 37, 1689-1695.
19. Wang, M.; Gao, M.; Mock, B. H.; Miller, K. D.; Sledge, G. W.; Hutchins, G. D.; Zheng, Q.-H. Synthesis of carbon-11 labeled fluorinated 2-arylbenzothiazoles as novel potential PET cancer imaging agents. Bioorg. Med. Chem. 2006, 14, 8599-8607.
20. Kadri, H.; Matthews, C. S.; Bradshaw, T. D.; Stevens, M. F. G.; Westwell, A. D. Synthesis and antitumour evaluation of novel 2-phenylbenzimidazoles. J. Enzyme Inhib. Med. Chem., in press.
21. Evindar, G.; Batey, R. A. Parallel synthesis of a library of benzoxazoles and benzothiazoles using ligand-accelerated copper-catalysed cyclizations of ortho-halobenzanilides. J. Org. Chem. 2006, 71, 1802-1808.
22. Hutchinson, I.; Stevens, M. F. G.; Westwell, A. D. The regiospecific synthesis of 5- and 7-monosubstituted and 5,6-disubstituted 2-aryl- benzothiazoles. Tetrahedron Lett. 2000, 41, 425-428.
23. Fried, K. W.; Bazzi, R.; Lopez, W. L.; Corsten, C.; Schramm, K.-W.; Bell, D. R.; Rozman, K. K. Relationship between aryl hydrocarbon receptor-affinity and the induction of EROD activity by 2,3,7,8-tetrachlorinated phenothiazine and derivatives. Toxicol. Appl. Pharmacol. 2007, 224, 147-155.
24. Merchant, M.; Krishnan, V.; Safe, S. Mechanism of action of alpha-naphthoflavone as an Ah receptor antagonist in MCF-7 human breast cancer cells. Toxicol. Appl. Pharmacol. 1993, 120, 179-185.