Polyphenol proteasome inhibitors, synthesis, and methods of use

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Ester doai

Reexamination Certificate

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Reexamination Certificate



The present invention relates to synthetic green tea derived polyphenolic compounds, their modes of syntheses, and their use in inhibiting proteasomal activity and in treating cancers. The present invention is also directed to pharmaceutical compositions useful in methods of inhibiting proteasomes and of treating cancers.

patent: 6713506 (2004-03-01), Dou et al.
patent: 7038048 (2006-05-01), Lu et al.
Adams, J. et al. “Proteasome inhibitors: A novel class of potent and effective antitumor agents”Cancer Res., 1999, 59:2615-2622.
Almond, J.B. and G.M. Cohen “The proteasome: a novel target for cancer chemotherapy”Leukemia, 2002, 16:433-443.
Dou, Q.P. et al. “Interruption of tumor cell cycle progression through proteasome inhibition: implications for cancer therapy”Prog. Cell Cycle Res., 2003, 5:441-446.
Dou, Q.P. And B. Li “Proteasome inhibitors as potential novel anticancer agents”Drug Resis. Updates, 1999, 2:215-223.
Kazi, A. et al. “Inhibition of the proteasome activity, a novel mechanism associated with the tumor cell apoptosis-inducing ability of genistein”Biochem. Pharm., 2003, 66:965-976.
Kazi, A. et al. “A naturalmusaceasplant extract inhibits proteasome activity and induces apoptosis selectively in human tumor and transformed, but not normal and non-transformed, cells”Inter. J. Mol. Med., 2003, 12:879-887.
Kisselev, A. and A.L. Goldberg “Proteasome inhibitors: from research tools to drug candidates”Chem.&Biol., 2001, 8:739-758.
Li, B. and Q.P. Dou “Bax degradation by the ubiquitin/proteasome-dependent pathway: Involvement in tumor survival and progression”PNAS, 2000, 97(8):3850-3855.
Nam, S. et al. “Ester bond-containing tea polyphenols potently inhibit proteasome activity in vitro and in vivo”J. Biol. Chem., 276:13322-13330.
Pagano, M. et al. “Role of the ubiquitin-proteasome pathway in regulating abundance of the cyclin-dependent kinase inhibitor p27”Science, 1995, 269:682-685.
Verma, I.M. et al. “Rel/Nf-kB/IkB family: intimate tales of association and dissociation”Genes&Devel., 1995, 9:2723-2735.
Kazi, A. et al “Inhibition of Bcl-XLphosphorylation by tea polyphenols or epigallocatechin-3-gallate is associated with prostate cancer cell apoptosis”Mol. Pharmacology, 2002, 62(4):765-771.
Kazi, A. et al. “Potential molecular targets of tea polyphenols in human tumor cells: significance in cancer prevention” In Vivo, 2002, 16(6):397-403.
Smith, D.M. et al. “Docking studies and model development of tea polyphenol proteasome inhibitors: Applications to rational drug design”Proteins, 2004, 54:58-70.
Smith, D.M. et al. “Synthetic analogs of green tea polyphenols as proteasome inhibitors”Mol. Med., 2002, 8(7):382-392.
Smith, D.M. and Dou, Q.P. “Green tea polyphenol epigallocatechin inhibits DNA replication and consequently induces leukemia cell apoptosis”Int. J. Mol. Med., 2001, 7(6):645-652.
Chen, C. et al. “Activation of antioxidant-response element (ARE), mitogen-activated protein kinases (MAPKs) and caspases by major green tea polyphenol components during cell survival and death”Arch. Pharm. Res., 2000, 23(6):605-612.
Chung, J.Y. et al. “Mechanisms of inhibition of the Ras-MAP kinase signaling pathway in 30.7b Ras 12 cells by tea polyphenols (−)-epigallocatechin-3-gallate and theaflavin-3,3′-digallate”FASEB J., 2001, 15:2022-2024.
Masuda, M. et al. “Effects of epigallocatechin-3-gallate on growth, epidermal growth factor receptor signaling pathways, gene expression, and chemosensitivity in human head and neck squamous cell carcinoma cell lines”Clin. Cancer Res., 2001, 7:4220-4229.
Yang, C.S. and Wang, Z-Y “Tea and Cancer”J. Natl. Cancer Inst., 1993, 85(13):1038-1049.
Yu, R. et al. “Activation of mitogen-activated protein kinases by green tea polyphenols: potential signaling pathways in the regulation of antioxidant-responsive element-mediated Phase II enzyme gene expression”Carcinogenesis, 1997, 18(2):451-456.
Litkei, G. et al. “Flavonoids. XXV. Reaction of 2′-OR-chalcone dibromide with ammonia. Preparation of chalcone aziridine and 3-aminoflavanone”Acta Chimica Academiae Scientiarum Hungaricae, 1973, 76(1):95-105, abstract.
Haslam, E. et al. “Gallotannins. Part I. Introduction: and the Fractionation of Tannase” and “Gallotannins. Part II. Some Esters and Depsides of Gallic Acid”J. Chem. Soc., 1961, 1829-1835 & 1836-1842.
Nam, S. et al. “Tannic acid potently inhibits tumor cell proteasome activity, increases p27 and Bax expression, and induces G1arrest and apoptosis”Cancer Epidemiology, Biomarkers&Prevention, 2001, 10:1083-1088.
Cerbai, G. et al. “Amides of substituted benzoic and cinnamic acids”Gazzetta Chimica Italiana, 1962, 92:420-427, abstract.


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