Flavonoids: Recent advances as anticancer drugs

Recent Patents on Anti-Cancer Drug Discovery

Volumn 5, Issue 2, 2010, Pages 152-164

  Liu, Hai L ^a   Jiang, Wen B ^a   Xie, Meng X ^a  

^a BEIJING NORMAL UNIVERSITY   (China)

Author keywords

Anthocyanin; Anticancer; Chalcone; Flavanol; Flavones; Flavonoids; Flavonol; Isoflavone; Synthetic analogue

Indexed keywords

2',3 DINITROFLAVONE 8 ACETIC ACID; 3 ALKOXYXANTHONE DERIVATIVE; 5,6 DIMETHYLXANTHENONE 4 ACETIC ACID; 6 ALKOXYXANTHONE DERIVATIVE; ANTHOCYANIN; ANTINEOPLASTIC AGENT; APIGENIN; BORONIC CHALCONE; CHALCONE COUMARIN; CHALCONE DERIVATIVE; EPICATECHIN GALLATE; EPIGALLOCATECHIN; EPIGALLOCATECHIN GALLATE; FLAVANOL DERIVATIVE; FLAVONE; FLAVONOID; GENISTEIN; GREEN TEA CATECHIN; ISOFLAVONE; KAEMPFEROL; MITOFLAXONE; MYRICETIN; NONSTEROID ANTIINFLAMMATORY AGENT; PLATINUM COMPLEX; PROANTHOCYANIDIN; QUERCETIN; SL 0101; UNCLASSIFIED DRUG; UNINDEXED DRUG; XANTHOHUMOL; XANTHONE 4 ACETIC ACID; FLAVONE DERIVATIVE; FLAVONOL DERIVATIVE;

ANTIFUNGAL ACTIVITY; ANTIINFLAMMATORY ACTIVITY; ANTINEOPLASTIC ACTIVITY; ARTICLE; BINDING AFFINITY; BONE CANCER; BREAST CANCER; CANCER INHIBITION; CLINICAL TRIAL; DRUG POTENCY; DRUG POTENTIATION; DRUG PROTEIN BINDING; DRUG STRUCTURE; GROWTH INHIBITION; HUMAN; LEUKEMIA; MULTIPLE CANCER; NONHUMAN; OSTEOPOROSIS; PRIORITY JOURNAL; PROSTATE CANCER; PROSTATE HYPERTROPHY; STRUCTURE ACTIVITY RELATION; ANIMAL; BIOLOGICAL MODEL; EVALUATION; LEGAL ASPECT; NEOPLASM; ONCOLOGY; PATENT; REVIEW;

ANIMALS; ANTHOCYANINS; ANTINEOPLASTIC AGENTS; CHALCONES; FLAVONES; FLAVONOIDS; FLAVONOLS; HUMANS; MEDICAL ONCOLOGY; MODELS, BIOLOGICAL; NEOPLASMS; PATENTS AS TOPIC;

EID: 77952959798     PISSN: 15748928     EISSN: None     Source Type: Journal    
DOI: 10.2174/157489210790936261     Document Type: Article

References (188)

1. Newman DJ, Cragg GM. Natural products as sources of new drugs over the period 1981-2002. J Nat Prod 2003; 66: 1022-37.
2. Butle MS. The role of natural product chemistry in drug discovery. J Nat Prod 2004; 67: 2141-53.
3. Newman DJ, Cragg GM. Natural products as sources of new drugs over the last 25 years. J Nat Prod 2007; 70: 461-77.
4. Ren W, Qiao Z, Wang H, Zhu L, Zhang L. Flavonoids: Promising anticancerragents. Med Res Rev 2003; 23: 519-34.
5. Ramos S. Effects of dietary flavonoids on apoptotic pathways related to cancer chemoprevention. J Nurt Biochem 2007; 18: 427-42.
6. Moon YJ, Wang X, Morris ME. Dietary flavonoids: effects on xenobiotic and carcinogen metabolism. Toxicol In Vitro 2006; 20: 187-210.
7. Kosmider B, Osiecka R. Flavonoid compounds: A review of anticancer properties and interactions with cis-diamminedichloro-platinum(ii). Drug Dev Res 2004; 63: 200-11.
8. Harborne JB, Williams CA. Advances in flavonoid research since 1992. Phytochemistry 2000; 55: 481-504.
9. Zhang HR, Wu XY. Study on the role of polysaccharide and flavone in Chinese herbs in protecting DNA with fluorescence probe. Spectrosc Spect Anal 2007; 27: 346-9.
10. Garavello W, Rossi M, McLaughlin JK, Bosetti C, Negri E, Lagiou P, et al. Flavonoids and laringea cancer risk in Italy. Ann Oncol 2007; 18: 1104-9.
11. Rossi M, Negri E, Talamini R, Bosetti C, Parpinel M, Gnagnarella P, et al. Flavonoids and colorectal cancer in Italy. Cancer Epidemiol Biomarkers Prev 2006; 15:1555-8.
12. Lahey, T. P., Rajadhyaksha, V. J. Inhibition by 3-deoxyflavonoids of T-lymphocyte activation and therapies related thereto. US20040209825 (2004).
13. Lahey, T. P., Rajadhyaksha, V. J. Inhibition by deoxyflavonoids of T-lymphocyte actiovation and therapies related thereto. US20040209825 (2004).
14. Nakanishi, K., Yanase, E., Sparrow, J. R. Antioxidant flavonoid derivatives. WO2009064485 (2009).
15. Segawa, S., Yasui, K., Yasui, N., Kurihara, T. Antiallergic composition. US2009028970 (2009).
16. Kwon, D. H., Choi, W. J., Lee, C. H., Kim, J. H., Kim, M. B. Flavonoid compound having an antiviral activity. US2009171074 (2009).
17. Pietta PG. Flavonoids as antioxidants. J Nat Prod 2000; 63: 1035-42.
18. Xie MX, Xu XY, Wang YD. Interaction between hesperetin and human serum albumin revealed by spectroscopic methods. Biochim Biophys Acta Gen Subj 2005; 1724: 215-24.
19. Amin A, Buratovich M. The anti-cancer charm of flavonoids: A cup-of-tea will do! Recent Pat Anti-Cancer Drug Discov 2007; 2: 109-17.
20. Kale A, Gawande S, Kotwal S. Cancer phytotherapeutics: role for flavonoids at the cellular level. Phytother Res 2008; 22: 567-77.
21. Morley, K., Koropatnick, J., Guthrie, N. The use of flavonoids for the inhibition of cellular growth. WO2008035208 (2008).
22. Udell, R. G. Soft gel capsules containing polymethoxylated flavones and palm oil tocotrienols. US20050249803 (2005).
23. Ahrens, M. J., Thompson, D. L. Composition and method for treating diabetes and metabolic disorders. US20080234364 (2008).
24. Theoharides, T. C. Compositions for protection against superficial vasodilator flush syndrome, and methods of use. WO2009076353 (2009).
25. Rosenbloom, R. A. Compositions and methods for treatment of rhinovirus. US7405046 (2008).
26. Barlow, C., Carter, T., Morse, A., Treuner, K., Lorrain, K. I. Modulation of neurogenesis with biguanides and GSK3-beta agents. US20080188457 (2008).
27. Barlow, C., Carter, T., Morse, A., Treuner, K., Lorrain, K. I. PPAR mediated modulation of neurogenesis. US20080103165 (2008).
28. Papadopoulou A, Green RJ, Frazier RA. Interaction of flavonoids with bovine serum albumin: a fluorescence quenching study. J Agric Food Chem 2005; 53: 158-63.
29. Qin C, Xie MX, Liu Y. Characterization of the myricetin-human serum albumin complex by spectroscopic and molecular modeling approaches. Biomacromolecules 2007; 8: 2182-9.
30. Su Z, Qin C, Xie MX, Li JD, Wang JD. Monomeric and oligomeric flavanols are agonists of membrane androgen receptors. Acta Chim Sin 2007; 65: 329-36.
31. Aron PM, Kennedy JA. Flavan-3-ols: Nature, occurrence and biological activity. Mol Nutr Food Res 2008; 52: 79-104.
32. Boumendjel A, Di Pietro A, Dumontet C, Barron D. Recent advances in the discovery of flavonoids and analogs with high-affinity binding to P-glycoprotein responsible for cancer cell multidrug resistance. Med Res Rev 2002; 22: 512-29.
33. Chen IL, Chen JY, Shieh PC, Chen JJ, Lee CH, Juang SH, et al. Synthesis and antiproliferative evaluation of amide-containing flavone and isoflavone derivatives. Bioorg Med Chem 2008; 16: 7639-45.
34. Kim YW, Mobley JA, Brueggemeier RW. Synthesis and estrogen receptor binding a nities of 7-Hydroxy-3-(4-hydroxyphenyl)-4H-1-benzopyran-4-ones containing a basic side chain. Bioorg Med Chem Lett 2003; 13: 1475-8.
35. Kim YW, Hackett JC, Brueggemeier RW. Synthesis and aromatase inhibitory activity of novel pyridine-containing isoflavones. J Med Chem 2004; 47: 4032-40.
36. Siddique YH, Beg T, Afzal M. Antigenotoxic effect of apigenin against anti-cancerous drugs. Toxicol In Vitro 2008; 22: 625-31.
37. Liu, Y. Safe natural pharmaceutical composition for treating cancer. US20040072790 (2004).
38. Van Helvoort, A. L. B., Van Norren, K., Gros-Van, H. M., Lansink, M. Preparation for the prevention and or treatment of altered bone metabolism. US20040152640 (2004).
39. Agrawal A, Yang J, Murphy RF, Agrawal DK. Regulation of the p14ARF-Mdm2-p53 pathway: An overview in breast cancer. Exp Mol Pathol 2006; 81: 115-22.
40. Walle, T., Halushka, P. V. A method of treating colon cancer by administering apigenin, luteolin, diosmetin and crysin. WO2001058410 (2001).
41. Lee SH, Ryu JK, Lee KY, Woo SM, Park JK, Yoo JW, et al. Enhanced anti-tumor effect of combination therapy with gemcitabine and apigenin in pancreatic cancer. Cancer Lett 2008; 259: 39-49.
42. Jiang, B. H., Fang, J. Apigenin for chemoprevention, and chemotherapy combined with therapeutic reagents. US20060189680 (2006).
43. Min LW. New therapeutic aspects of flavones: The anticancer properties of Scutellaria and its main active constituents Wogonin, Baicalein and Baicalin. Cancer Treat Rev 2009; 35: 57-68.
44. Perez CA, Wei Y, Guo M. Iron-binding and anti-Fenton properties of baicalein and baicalin. J Inorg Biochem 2009; 103: 326-32.
45. Ding XF, Gao HN, Guo XH, Wang ZZ, Yang LH, Guan Y, et al. Analysis of the 4th generation scutellaria baicalensis georgi with space mutagenesis via ftir spectroscopy. Spectrosc Spect Anal 2009; 29: 1286-8.
46. Li YX, Suo QL, He WZ, Li CP, Huang YC. Separation and purification and structural characterization of baicalein. Spectrosc Spect Anal 2008; 28: 1895-9.
47. You, Q. Z. Application of wogonin in the preparing of medicine for treating gastric cancer. CN101062029 (2007).
48. Wu, Y. The synergistically pharmaceutical composition of baicalein and baicalin for inhibiting tumor. EP1849467 (2007).
49. Zhao, X. X. Plant drug for preventing cancer. US2003180391 (2003).
50. Hsu, L., Chang, S., Shen, C., Liao, Y., Chuang, K. Flavone derivatives as TNFalpha inhibitors or antagonists. US20060105967 (2006).
51. Gesson, J., Fonteneau, N., Mondon, M., Charbit, S., Ficheux, H., Schutze, F. 7-Carboxy-flavone derivatives preparation method and therapeutic use. US6965039 (2005).
52. Donovan, R. M., Green, M. R., Tasker, M. C., Yates, P. R. Use of prenylated flavones. US6589982 (2003).
53. Atassi G, Briet P, Berthelon JJ, Collonges F. Synthesis and antitumor activity of some 8-substituted-4-oxo-4H-1-benzopyrans. Eur J Med Chem Chim Ther 1985; 20: 393-402.
54. Corbett TH, Bissery M, Wozniak A, Plowman J, Polin L, Tapazoglou E, et al. Activity of flavone acetic acid (NSC-347512) against solid tumors of mice. Invest New Drugs 1986; 4: 207-20.
55. Kerr DJ, Kaye SB. Flavone acetic acid - preclinical and clinical activity. Eur J Cancer Clin Oncol 1989; 25: 1271-2.
56. Valenti P, Bisi A, Rampa A, Belluti F, Gobbi S, Zampiron A, et al. Synthesis and biological activity of some rigid analogues of flavone-8-acetic acid. Bioorg Med Chem 2000; 8: 239-46.
57. Lee, K.-H., Xia, Y., Yang, Z.-Y., Bastow, K. F., Kuo, S.-C. Flavone acetic acid analogs and methods of use thereof. US2004167151 (2004).
58. Fukasawa K, Fujii H, Saitoh Y, Koizumi K, Aozuka Y, Sekine K, et al. Aminopeptidase N (APN/CD13) is selectively expressed in vascular endothelial cells and plays multiple roles in angiogenesis. Cancer Lett 2006; 243: 135-43.
59. Bauvois B, Puiffe ML, Bongui JB, Paillat S, Monneret C, Dauzonne D. Synthesis and biological evaluation of novel flavone-8-acetic acid derivatives as reversible inhibitors of aminopeptidase n/cd13. J Med Chem 2003; 46: 3900-13.
60. Rewcastle GW, Atwell GJ, Baguley BC, Calveley SB, Denny WA. Potential antitumor agents.58.synthesis and structure-activity relationships of substituted xanthenone-4-acetic acids active against the colon 38 tumor in vivo. J Med Chem 1989; 32: 793-9.
61. Rewcastle GW, Atwell GJ, Palmer BD, Boyd PD, Baguley BC, Denny WA. Potential antitumor agents. 62. Structure-activity relationships for tricyclic compounds related to the colon tumor active drug 9-0~0-9h-xanthene-4-acetic acid. J Med Chem 1991; 34: 491-96.
62. Rewcastle GW, Atwell GJ, Li ZA, Baguley BC, Denny WA. Potential antitumor agents. 61.structure-activity relationships for in vivo colon 38 activity among disubstituted 9-0~0-9h-xanthene-4-acetic acids. J Med Chem 1991; 34: 217-22.
63. Cai SX. Small molecule vascular disrupting agents: Potential new drugs for cancer treatment. Recent Pat Anticancer Drug Discov 2007; 2: 79-101.
64. Baguley, B. C., Ching, L. M., Philpott, M. Cancer treatment by combination therapy. US7510830 (2009).
65. Krissansen, G. W., Kanwar, J. R., Ching, L.-M. Cancer therapy. US2003003092 (2003).
66. Baguley, B. C., Ching, L., Kestell, P., Zhao, L. Anti-cancer composition comprising DMXAA or related compound. US7585893 (2009).
67. Vogel, S. N., Roberts, Z. J., Cole, L. E. Use of 5,6-dimethylxanthenone-4-acetic acid as an antimicrobial agent. WO2008147445 (2008).
68. Baguley BC. Antivascular therapy of cancer: DMXAA. Lancet Oncol 2003; 4: 141-8.
69. Zhao L, Ching LM, Baguley BC. Kestell P, Kelland LR. Mechanisms of tumor vascular shutdown induced by 5,6-dimethylxanthenone-4-acetic acid (DMXAA): Increased tumor vascular permeability. Int J Cancer 2005; 116: 322-6.
70. McKeage MJ, Reck M, Jameson MB, Rosenthal MA, Gibbs D, Mainwaring PN, et al. Phase II study of ASA404 (vadimezan, 5,6-dimethylxanthenone-4-acetic acid/DMXAA) 1800mg/m(2) combined with carboplatin and paclitaxel in previously untreated advanced non-small cell lung cancer. Lung Cancer 2009; 65: 192-7.
71. Gabra H, Jameson M. Update of phase II study of DMXAA (AS1404) combined with carboplatin and paclitaxel in recurrent ovarian cancer. Ejc Suppl 2007; 5: 319-9.
72. Liu JJ, Ching LM, Goldthorpe M, Sutherland R, Baguley BC, Kirker JA, et al. Cancer Chemother Pharmacol 2007; 59: 661-9.
73. Wang LCS, Ching LM, Baguley BC, Paxton JW, Kestell P, Zhuang L, et al. Enhancement of the action of the antivascular drug 5,6-dimethylxanthenone-4-acetic acid (DMXAA; ASA404) by non-steroidal anti-inflammatory drugs. Invest New Drugs 2009; 27: 280-84.
74. Wang, L.-C. S., Paxton, J. W., Ching, L.-M., Baguley, B. C., Kestell, P. Anti-cancer combinations. US7462642 (2008).
75. Wilson, W. R., Siim, B. G. Anti-cancer combinations. US20080070848 (2008).
76. Gobbi S, Rampa A, Bisi A, Belluti F, Piazzi L, Valenti P, et al. Synthesis and antitumor activity of new derivatives of xanthen-9-one-4-acetic acid. J Med Chem 2002; 45: 4931-9.
77. Gobbi S, Belluti F, Bisi A, Piazzi L, Rampa A, Zampiron A, et al. New derivatives of xanthenone-4-acetic acid: Synthesis, pharmacological profile and e ect on TNF-a and NO production by human immune cells. Bioorg Med Chem 2006; 4101-9.
78. Campbell M, Progress in the evaluation of CDK inhibitors as anti-tumor agents. Drug Discovery Today 2008; 13: 875-81.
79. Hong, C. Y., Park, T. S., Kim, Y. K., Lee, J. H., Kim, J. H., Kim, D. M., Son, H. S., Kim, S. W., Kim, E. E. K. CDK inhibitors having flavone structure. US6500846 (2002).
80. Haesslein, J., Lefrancois, D., Uridat, E., Zhang, J. Flavone derivatives, preparation method and use as medicines. US20030119816 (2003).
81. Lal, B., Joshi, K., Kulkarni, S., Mascarenhas, M., Kamble, S., Rathos, M. J., Joshi, R., Sivakumar, M. Inhibitors of cyclin dependent kinases and their use. US20070015802 (2007).
82. Sivakumar, M., Mascarenhas, M., Sarde, A., Jadhav, P. K., Shukla, M., Joshi, K., Rathos, M. Enantiomerically pure flavone derivatives for the treatment of poliferative disorders and processes for their preparation. WO2007148158 (2007).
83. Szkudelska K, Nogowski L. Genistein - A dietary compound inducing hormonal and metabolic changes. J Steroid Biochem Mol Biol 2007; 105: 37-45.
84. Kelly, G. E., Joannou, G. E. Therapeutic methods and compositions involving isoflavones. WO9808503 (1998).
85. Taylor, R. B., Henley, E. C. Composition for and method of preventing or treating breast cancer. US6300367 (2001).
86. Thurn, M. J., Huang, L. J. Methods for treating cancer with legume plant extracts. US6004558 (1999).
87. Sarkar, F., Padhye, S. Flavanone compound and uses thereof. US7256214 (2007).
88. Wang BF, Wang JS, Lu JF, Kao TH, Chen BH. Antiproliferation effect and mechanism of prostate cancer cell lines as affected by isoflavones from soybean cake. J Agric Food Chem 2009; 57: 2221-32.
89. Dixon RA, Ferreira D. Genistein. Phytochemistry 2002; 60: 205-11.
90. Empie, M., Gugger, E. Method of preparing and using compositions extracted from vegetable matter for the treatment of cancer. US6900240 (2005).
91. Kelly, G. E. Health supplement. US6987098 (2006).
92. Wei, H. Genistein as a preventive against ultraviolet induced skin photo damage and cancer. US5824702 (1998).
93. Barnes, S., Blair, H. C. Genistein for use in inhibiting osteroclasts. US5506211 (1996).
94. Schoenmakers, I., Dang, Z., Lowik, C. W. G. M., Van Helvoort, A. L. B., Hageman, R. J. J., Gros-van, M. H. Method of treating mammals with genistein and/or genistein analogues. US20050090457 (2005).
95. Rodriguez, G. C. Pharmaceutical product containing progestin, genistein, and vitamin D compound. US20080167276 (2008).
96. Uckun, F. M. EGF-genistein conjugates for the treatment of cancer. US5911995 (1999).
97. Uckun, F. M. Use of EGF genistein to prevent development of EGF-receptor expressing cancers. US20020193319 (2002).
98. Xu, X., Yuan, C., Wang, J., Oi, S., Yin, H., Zeng, Y. Isoflavone derivatives of tectoridin, the preparation thereof and the anti-virus medicines containing the same as an effective constituents. US2007123566 (2007).
99. Burdet, B., Ruettimann, A. Manufacture of isoflavones. WO2004009576 (2004).
100. Harms, A. E. Synthesis of isoflavone. US20090062555 (2009).
101. Liao, D., Zheng, X., Zhu, B. Novel isoflavone nicotinic acid ester derivatives, preparing method and use thereof. CN101210012 (2008).
102. Brueggemeier, R. W., Kim, Y.-W. 2-Heterosubstituted 3-aryl-4H-1-benzopyran-4-ones as novel therapeutics in breast cancer. US20060293321 (2006).
103. Kim YW, Brueggemeier RW. A convenient one-pot synthesis of 2-(alkylthio)isoflavones from deoxybenzoins using a phase transfer catalyst. Tetrahedron Lett 2002; 43: 6113-5.
104. Balunas MJ, Su B, Brueggemeier RW, Kinghorn AD. Natural products as aromatase inhibitors. Anticancer Agents Med Chem 2008; 8: 646-82.
105. Geiser J, Lønning PE. Endocrine effects of aromatase inhibitors and inactivators in vivo: Review of data and method limitations. J Steroid Biochem Mol Biol 2005; 95: 75-81.
106. Le Bail JC, Laroche T, Marre-Fournier F, Habrioux G. Aromatase and 17 -hydroxysteroid dehydrogenase inhibition by flavonoids. Cancer Lett 1998; 133:101-6.
107. Brueggemeier, R. W., Kim, Y.-W., Hackett, J. C. Heteroaryl-containing isoflavones as aromatase inhibitors. WO2007001348 (2007).
108. Chung, K.-H., Oh, S.-M., Kim, Y.-P. Drug for osteoporosis having inhibition effect on cancer comprising Ginkgo biloba extracts as the active ingredient. WO2005077396 (2005).
109. Gokaraju, G. R., Gokaraju, R. R., Gottumukkala, V. S., Golakoti, T. Dietary supplement formulation for controlling inflammation and cancer. US7455860 (2008).
110. Murakami A, Ashida H, Terao J. Multitargeted cancer prevention by quercetin. Cancer Lett 2008; 269: 315-25.
111. Xie MX, Long M, Liu Y, Qin C, Wang YD. Characterization of the interaction between human serum albumin and morin. Biochim Biophys Acta Gen Subj 2006; 1760: 1184-91.
112. Harwood M, Danielewska-Nikiel B, Borzelleca JF, Flamm GW, Williams GW, Lines TC. A critical review of the data related to the safety of quercetin and lack of evidence of in vivo toxicity, including lack of genotoxic/carcinogenic properties. Food Chem Toxicol 2007; 45: 2179-2205.
113. Erlund I. Review of the flavonoids quercetin, hesperetin, and naringenin. Dietary sources, bioactivities, bioavailability, and epidemiology. Nutr Res 2004; 24: 851-74
114. Walle, T. Use of quercetin and resveratrol to treat and prevent oral cancer. WO2005082407 (2005).
115. Park, Y.-M., Baek, S.-H., Han, M.-Y., Choi, E.-M., Lee, C.-W., Kim, J.-W., Park, J.-H. Method for inhibiting VEGF and EPO gene expression by quercetin. WO02057473 (2002).
116. Smith JA, Poteet-Smith CE, Hecht SM, Xu Y, Errington TM, Lannigan DA. Identification of the first specific inhibitor of p90 ribosomal S6 kinase (RSK) reveals an unexpected role for RSK in cancer cell proliferation. Cancer Res 2005; 65: 1027-34.
117. Maloney DJ, Hecht SM. Synthesis of a potent and selective inhibitor of p90 rsk. Org Lett 2005; 7: 1097-9.
118. Smith JA, Maloney DJ, Clark DE. Influence of rhamnose substituents on the potency of SL0101, an inhibitor of the Ser/Thr kinase, RSK. Bioorg Med Chem 2006; 14: 6034-42.
119. Tückmantel W, Kozikowski AP, Romanczyk Jr LJ. Studies in polyphenol chemistry and bioactivity. 1. preparation of building blocks from (+)-catechin. Procyanidin formation. synthesis of the cancer cell growth inhibitor, 3-o-galloyl-(2r,3r)-epicatechin-4â,8-[3-o-galloyl-(2r,3r)-epicatechin]. J Am Chem Soc 1999; 121: 12073-81.
120. Nifli AP, Bosson-Kouamé A, Papadopoulou N. Monomeric and oligomeric flavanols are agonists of membrane androgen receptors. Exp Cell Res 2005; 309: 329-39.
121. Dodo K, Minato T, Noguchi-Yachide T. Antiproliferative and apoptosis-inducing activities of alkyl gallate and gallamide derivatives related to (-)-epigallocatechin gallate. Bioorg Med Chem 2008; 16: 7975-82.
122. Kuzuhara T, Suganuma M, Fujiki H. Green tea catechin as a chemical chaperone in cancer prevention. Cancer Lett 2008; 261: 12-20.
123. Morre, D. M., Morre, D. J., Cooper, R., Sun, H., Ye, Q. Tea catechin formulations and processes for making same. US6428818 (2002).
124. Morre, D. M., Morre, D. J. Tea catechins as cancer specific proliferation inhibitors. US6652890 (2003).
125. Buxton, I. Polyphenol inhibition of nucleoside diphosphate kinase-B activity and cancer metastasis. US20030175834 (2003).
126. Simmons, D. L., Dong, C. Liquid compositions comprising non-digestible oligosaccharides and green tea catechins, method and uses thereof. US20040047921 (2004).
127. Memarzadeh, B., Bowman, L. Reagents and methods to treat ocular diseases and infection. WO2008054639 (2008).
128. Kamberling, J. K., Selman, S. H. Compositions and methods for perioperative bladder instillation. US20090227669 (2009).
129. Lee, I., Ahn, W., Hara, Y. Chemical composition for treating cervical intraepithelial neoplasia I, II, III, IV and cervicitis. WO0033832 (2000).
130. Chung, F. L. Inhibition of lung tumorigenesis by administration of a polyphenol. US5391568 (1995).
131. Navarro-Perán E, Cabezas-Herrera J, del Campo LS. Effects of folate cycle disruption by the green tea polyphenol epigallocatechin-3-gallate. Int J Biochem Cell Biol 2007; 39: 2215-25.
132. Rodriguez-Lopez, J. N., Navarro-Peran, E. M., Cabezas-Herrera, J. Dihydrofolate reductase inhibition by epigallocatechin gallate compounds. US20070249545 (2007).
133. Rodriguez-Lopez, J. N., Cabezas-Herrera, J., Navarro-Peran, E. M., Sanchez, D. C. L. Epigallocatechin-3-gallate compositions for cancer therapy and chemoprotection. WO2008075201 (2008).
134. Morre, D. M., Morre, D. J. Compositions based on vanilloid-catechin synergies for prevention and treatment of cancer. US20030072821 (2003).
135. Netke, S., Niedzwiecki, A., Rath, M., Roomi, W. M. Nutrient pharmaceutical formulation comprising polyphenols and use in treatment of cancer. US7041699 (2006).
136. Rath, M., Netke, S., Niedzwiecki, A. A nutrient pharmaceutical formulation comprising polyphenols and use in treatment of cancer. WO03057201 (2003).
137. Nandakumar V, Singh V, Katiyar SK. Multi-targeted prevention and therapy of cancer by proanthocyanidins. Cancer Lett 2008; 269: 378-87.
138. Larson, D. Catechin multimers as therapeutic drug delivery agents. WO03092613 (2003).
139. Ramljak, D., Romanczyk Jr., L. J., Dickson, R. B. Methods and compositions for treating cancer. US20050171029 (2005).
140. Romanczyk Jr., L. J., Hammerstone Jr., J. F., Buck, M. M. Antineoplastic cocoa extracts and methods for making and using the same. US5554645 (1996).
141. Alberte, R. S.; Roschek Jr., W. P. Antiinfective proanthocyanidin compounds and methods of use thereof. US20090130128 (2009).
142. Rozhon, E. J., Khandwala, A. S., Sabouni, A., Balwani, G. P., Chan, J. W., Sesin, D. F. Compositions and methods of treatment with proanthocyanidin polymer antidiarrheal compositions. US20090148397 (2009).
143. Kemberling, K. J., Selman, S. H. Polyphenols as an intravesical agent for the prevention of transitional cell tumor implantation. US20050165090 (2005).
144. Mastrodonato, M., Ciattini, R. Compositions and methods for the treatment of inflammatory conditions of the mucosae, skin and the eye. US20080015155 (2008).
145. Snow, A. D., Castillo, G. M., Choi, P. Y., Nguyen, B. P. Proanthocyanidins for the treatment of amyloid and alpha-synuclein diseases. US20030017998 (2003).
146. Nonaka, G., Sun, B., Yuan, L., Nakagawa, T., Fujii, H., Surh, Y. Sulfur-containing proanthocyanidin oligomer compositon and process for producing the same. US20050261198 (2005).
147. 1 establishment of interflavan linkage regio- and stereochemistry by oxidative degradation of an o-alkylated derivative of procyanidin b2 to (r)-(-)-2,4-diphenylbutyric acid. J Org Chem 2000; 65: 5371-81.
148. Kozikowski AP, Tückmantel W, Hu Y. Studies in polyphenol chemistry and bioactivity. 3.(1,2) stereocontrolled synthesis of epicatechin-4,8-epicatechin, an unnatural isomer of the b-type procyanidins. J Org Chem 2001; 66: 1287-96.
149. Kozikowski AP, Tückmantel W, Böttcher G, Hu Y. Studies in polyphenol chemistry and bioactivity. 4.(1) synthesis of trimeric, tetrameric, pentameric, and higher oligomeric epicatechin-derived procyanidins having all-4,8-interflavan connectivity and their inhibition of cancer cell growth through cell cycle arrest(1). J Org Chem 2003; 68: 1641-58.
150. Kozikowski, A. P., Tückmantel, W., Romanczyk Jr., L. J., Ma, X. Synthesis of oligomeric epicatechin and catechin-derived procyanidins. WO2004030440 (2004).
151. Kozikowski, A. P., Tückmantel, W., Romanczyk Jr., L. J. Synthesis of dimeric, trimeric, tetrameric, pentameric, and higher oligomeric epicatechin-derived procyanidins having 4beta, 8-interflavan linkages and their use to inhibit cancer cell growth through cell cycle arrest. US2006173198 (2006).
152. Thomasset S, Teller N, Cai H, Marko D, Berry DP, Steward WP, et al. Do anthocyanins and anthocyanidins, cancer chemopre-ventive pigments in the diet, merit development as potential drugs? Cancer Chemother Pharmacol 2009; 64: 201-11.
153. Wang LS, Stoner GD. Anthocyanins and their role in cancer prevention. Cancer Lett 2008; 269: 281-90.
154. Stockfleth, E. Use of a polyphenol for the treatment of a cancerous or precancerous lesion of the skin. US20070059387 (2007).
155. Taylor, R. B., Henley, E. C. Composition for and method of preventing or treating breast cancer. US20010047033 (2001).
156. Nair, M. G., Bourquin, L. D., Seeram, N. P., Kang, S. Method for treating tumors caused by APC gene mutation with anthocyanins and cyanidin. US6656914 (2003).
157. Magnuson, B. A., Giusti, M. M., Malik, M., Zhao, C. Anthocyanin-rich compositions and methods for inhibiting cancer cell growth. US20060159781 (2006).
158. Wang, C. Hibiscus anthocyanins for inhibiting cancers. US20060275521 (2006).
159. Wang, C. Hibiscus anthocyanins for inhibiting cancers. US20080113050 (2008).
160. Rose, S. D., Hartman, R. F. Modified chalcone compounds as antimitotic agents. CA2651983 (2007).
161. Park, K. H., Lee, J. W., Ryu, Y. B., Ryu, H. W., Lee, S. A. Method for screening anti-cancer compounds inhibiting functions of TM4SF5 and anti-cancer composition containing chalcone compounds. KR20080052391 (2008).
162. Bombardelli, E., Mancuso, S. B., Delle, M. F. Halcone complex having antiproliferation activity against tumors of uterine, ovarian and mammary. JP2004131509 (2004).
163. Zi, X., Simoneau, A. R. Treatment of bladder and urinary tract cancers. US7326734 (2008).
164. Himawari, H., Takaoka, S. Apoptosis inducting agent. JP2004107300 (2004).
165. Kozlowski D, Trouillas P, Calliste C, Marsal P, Lazzaroni R, Duroux JL. Density functional theory study of the conformational, electronic, and antioxidant properties of natural chalcones. J Phys Chem A 2007; 111: 1138-45.
166. Anto RJ, Sukumarana K, Kuttana G, Sukumaran K, Rao MNA, Subbaraju V. Anticancer and antioxidant activity of synthetic chalcones and related compounds. Cancer Lett 1995; 97: 33-7.
167. Ávila HP, Smânia EFA, Monache FD, Samania A. Structure-activity relationship of antibacterial chalcones. Bioorg Med Chem 2008; 16: 9790-4.
168. Rosen, R. T., Ho, C.-T., Dipaola, R. S., Rafi, M. M., Vastano, B., Ghai, G. Anti-carcinogenic activity of hydroxylated chalcone compounds extracted from licorice root. US20020022665 (2002).
169. Bombardelli, E., Mancuso, S., Delle, M. F. Chalcones and esters thereof with antiproliferative activity in uterus, ovary and breast tumors. US5808137 (1998).
170. Day, B. J. Methods for treatment of thiol-containing compound deficient conditions. US20080221029 (2008).
171. Rose, S. D., Hartman, R. F. Modified chalcone compounds as antimitotic agents. WO2007133588 (2007).
172. Boumendjel, A., Dumontet, C., Blanc, M., Mariotte, A.-M. Novel chalcone derivatives with antimitotic activity. US20090182058 (2009).
173. Kosmeder, J. W., Moriarty, R. M., Pezzuto, J. M., Song, L. L., Moon, R. C. Use of 4'-bromoflavone in a cancer chemopreventative composition and method. US6046231 (2000).
174. Park, K. H., Lee, J. W., Ryu, Y. B., Ryu, H. W., Lee, S.-A. Method for screening anti-cancer compounds inhibiting function of TM4SF5 and anti-cancer composition containing chalcone compounds. WO2008069608 (2008).
175. Bombardelli, E., Valenti, P. Chalcone coumarins. US2002161036 (2002).
176. Zhu, X., Liu, Z., Xie, B. Use of 2',4'-dihydroxy-6'-methoxy-3',5'-dimethyl chalcone for preparing anticancer medicine. CN1454895 (2003).
177. Quincoces, S. J. A., Peseke, K., Molina, R. R. Substituted acetophenonederivatives. EP1764363 (2007).
178. Hu, Y., Dong, X., Wei, E., Huang, X., Liu, T., Ma, Z. Carboxyl substituted chalcone derivative, preparation and use. CN101407457 (2009).
179. Agrawal A, Yang J, Murphy RF, Agarwal DK. Regulation of the p14ARF-Mdm2-p53 pathway: An overview in breast cancer. Exp Mol Pathol 2006; 81: 115-22.
180. Khan, S. R. Novel boronic chalcone derivatives and uses thereof. US2005176988 (2005).
181. Kumar SK, Hager E, Pettit C, Gurulingppa H, Davidson NE, Khan SR. Design, synthesis, and evaluation of novel boronic-chalcone derivatives as antitumor agents. J Med Chem 2003; 46: 2813-5.
182. Stevens JF, Page JE. Xanthohumol and related prenylflavonoids from hops and beer: To your good health! Phytochemistry 2004; 65: 1317-30.
183. Colgate EC, Miranda CL, Stevens JF, Bray TM, Ho E. Xanthohumol, a prenylflavonoidderived from hops induces apoptosis and inhibits NF-kappaB activation in prostate epithelial cells. Cancer Lett 2007; 246: 201-9.
184. Vanhoecke B, Derycke L, Van Marck V, Depypere H, De Keukeleire D, Bracke M. Antiinvasive effect of xanthohumol, a prenylated chalcone present in hops (Humulus lupulus L.) and beer. Int J Cancer 2005; 117: 889-95.
185. Ho, E., Stevens, J. F., Miranda, C. L., Buhler, D., Deinzer, M. L. Prostate cancer and benign prostatic hyperplasia treatments. US20080233221 (2008).
186. Khupse RS, Erhardt PW. Total synthesis of xanthohumol. J Nat Prod 2007; 70: 1507-9.
187. Erhardt, P. W., Khupse, R. S. Method for synthesizing xanthohumol. WO2009026206 (2009).
188. Galati G, O'Brien PJ. Potential toxicity of flavonoids and other dietary phenolics: Significance for their chemopreventive and anticancer properties. Free Radic Biol Med 2004; 37: 287-303.