The Relationship between Pharmacological Properties and Structure- Activity of Chrysin Derivatives

Author(s): Yang Li, Yan-peng Li, Jun He*, Ding Liu, Qi-zhi Zhang, Kang Li, Xing Zheng, Guo-Tao Tang, Yu Guo, Yunmei Liu*.

Journal Name: Mini-Reviews in Medicinal Chemistry

Volume 19 , Issue 7 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Chrysin is a natural product of a flavonoid compound. Chemically, chrysin consists of two phenyl rings (A and B) and a heterocyclic ring (C). Biologically, chrysin exerts many different physiological activities. In recent years, with the in-depth development for more active drugs, the synthesis and biological activities of chrysin derivatives have been well studied. Besides, structure-activity relationship of chrysin revealed that the chemical construction meets the critical chemical structural necessities of flavonoids for numerous pharmacological activities. It is generally believed that modified chrysin could be more potent than unmodified chrysin. Different modification in the rings of chrysin could possess various degrees of biological activities. This review aims to summarize the mechanism for the activities of chrysin and its derivatives in different rings. We also explored the relationship between biological function and structure-activity of substituted chrysin derivatives with different functional groups. The influence of chrysin derivatives on the proliferation and apoptosis of cancer cells is also investigated. Development of novel drugs based on the biological functions of chrysin could better improve clinical outcomes of affected population, especially for tumor patients and diabetic patients.

Keywords: Chrysin, chrysin derivatives, synthesis, biological activities, structure-activity relationships, drug target.

[1]
Zhang, S.; Wang, X.; Sagawa, K.; Morris, M.E. Flavonoids chrysin and benzoflavone, potent breast cancer resistance protein inhibitors,have no significant effect on topotecan pharmacokinetics in rats or mdr1a/1b (-/-) mice. Drug Metab. Dispos., 2005, 33, 341-348.
[2]
dos Santos, M.C.D.S.; Gonçalves, C.F.L.; Vaisman, M.; Ferreira, A.C.F.; de Carvalho, D.P. Impact of flavonoids on thyroid function. Food Chem. Toxicol., 2011, 49(10), 2495-2502.
[3]
Scalbert, A.; Williamson, G. Dietary intake and bioavailability of polyphenols. J. Nutr., 2000, 130(8), 2073S-2085S.
[4]
Suyenaga, E.S.; Konrath, E.L.; Dresch, R.R.; Apel, M.A.; Zuanazzi, J.A.; Chaves, C.G.; Henriques, A.T. Appraisal of the antichemotactic activity of flavonoids on polymorphonuclear neutrophils. Planta Med., 2011, 77(7), 698-704.
[5]
Zhao, D.Q.; Han, C.X.; Ge, J.T.; Tao, J. Isolation of a UDP-glucose: Flavonoid 5-O-glucosyltransferase gene and expression analysis of anthocyanin biosynthetic genes in herbaceous peony (Paeonia lactiflora Pall.). Electron. J. Biotechnol., 2012, 15(6), 9-9.
[6]
Lapidot, T.; Walker, M.D.; Kanner, J. Antioxidant and prooxidant effects of phenolics on pancreatic β-cells in vitro. J. Agric. Food Chem., 2002, 50(25), 7220-7225.
[7]
Pick, A.; Müller, H.; Mayer, R.; Haenisch, B.; Pajeva, I.K.; Weigt, M.; Bönisch, H.; Müller, C.E.; Wiese, M. Structure–activity relationships of flavonoids as inhibitors of breast cancer resistance protein (BCRP). Bioorg. Med. Chem., 2011, 19(6), 2090-2102.
[8]
Rahmanto, A.S.; Davies, M.J. Selenium‐containing amino acids as direct and indirect antioxidants. IUBMB Life, 2012, 64(11), 863-871.
[9]
Ahad, A.; Ganai, A.A.; Mujeeb, M.; Siddiqui, W.A. Chrysin, an anti-inflammatory molecule, abrogates renal dysfunction in type 2 diabetic rats. Toxicol. Appl. Pharmacol., 2014, 279(1), 1-7.
[10]
Chirumbolo, S.; Bjørklund, G. Chrysin and baicalin in diabetic nephropathy. Environ. Toxicol. Pharmacol., 2017, 51, 156-157.
[11]
Cushnie, T.T.; Lamb, A.J. Recent advances in understanding the antibacterial properties of flavonoids. Int. J. Antimicrob. Agents, 2011, 38(2), 99-107.
[12]
Yao, Y.; Chen, L.; Xiao, J.; Wang, C.; Jiang, W.; Zhang, R.; Hao, J. Chrysin protects against focal cerebral ischemia/reperfusion injury in mice through attenuation of oxidative stress and inflammation. Int. J. Mol. Sci., 2014, 15(11), 20913-20926.
[13]
Fahmi, A.I.; El-Shehawi, A.M.; Al-Otaibi, S.A.; El-Toukhy, N.M. Chemical analysis and antimutagenic activity of natural Saudi Arabian honey bee Propolis. Arab J. Biotechnol., 2011, 14(1), 25-40.
[14]
Kang, S.S.; Lee, J.Y.; Choi, Y.K.; Kim, G.S.; Han, B.H. Neuroprotective effects of flavones on hydrogen peroxide-induced apoptosis in SH-SY5Y neuroblostoma cells. Bioorg. Med. Chem. Lett., 2004, 14(9), 2261-2264.
[15]
Li, Y.; Yu, Z.; Liu, F.; Tan, L.; Wu, B.; Li, J. Oral glutamine ameliorates chemotherapy-induced changes of intestinal permeability and does not interfere with the antitumor effect of chemotherapy in patients with breast cancer: A prospective randomized trial. Tumori, 2006, 92(5), 396-401.
[16]
Zhang, T.; Chen, X.; Qu, L.; Wu, J.; Cui, R.; Zhao, Y. Chrysin and its phosphate ester inhibit cell proliferation and induce apoptosis in Hela cells. Bioorg. Med. Chem., 2004, 12(23), 6097-6105.
[17]
Habtemariam, S. Flavonoids as inhibitors or enhancers of the cytotoxicity of tumor necrosis factor-α in L-929 tumor cells. J. Nat. Prod., 1997, 60(8), 775-778.
[18]
Comte, G.; Daskiewicz, J.B.; Bayet, C.; Conseil, G.; Viornery-Vanier, A.; Dumontet, C.; Barron, D. C-Isoprenylation of flavonoids enhances binding affinity toward P-glycoprotein and modulation of cancer cell chemoresistance. J. Med. Chem., 2001, 44(5), 763-768.
[19]
Wongrattanakamon, P.; Lee, V.S.; Nimmanpipug, P.; Sirithunyalug, B.; Chansakaow, S.; Jiranusornkul, S. Insight into the molecular mechanism of p-glycoprotein mediated drug toxicity induced by bioflavonoids: An integrated computational approach. Toxicol. Mech. Methods, 2017, 27(4), 1-38.
[20]
Di Pietro, A.; Dayan, G.; Conseil, G.; Steinfels, E.; Krell, T.; Trompier, D.; Jault, J.M. P-glycoprotein-mediated resistance to chemotherapy in cancer cells: Using recombinant cytosolic domains to establish structure-function relationships. Braz. J. Med. Biol. Res., 1999, 32(8), 925-939.
[21]
Uhl, M.; Ecker, S.; Kassie, F.; Lhoste, E.; Chakraborty, A.; Mohn, G.; Knasmüller, S. Effect of chrysin, a flavonoid compound, on the mutagenic activity of 2-amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine (PhIP) and benzo (a) pyrene (B (a) P) in bacterial and human hepatoma (HepG2) cells. Arch. Toxicol., 2003, 77(8), 477-484.
[22]
Freeman, B.A.; Crapo, J.D. Biology of disease: Free radicals and tissue injury. Lab. Investig. J. Tech. Methods Pathol., 1982, 47(5), 412-426.
[23]
Lapidot, T.; Walker, M.D.; Kanner, J. Antioxidant and prooxidant effects of phenolics on pancreatic beta-cells in vitro. J. Agric. Food Chem., 2002, 50(25), 7220-7225.
[24]
Cushnie, T.P.; Lamb, A.J. Antimicrobial activity of flavonoids. Int. J. Antimicrob. Agents, 2005, 26, 343-356.
[25]
Ali, R.M.; Houghton, P.J.; Raman, A.; Hoult, J.R.S. Antimicrobial and antiinflammatory activities of extracts and constituents of Oroxylum indicum (L.) Vent. Phytomed., 1998, 5(5), 375-381.
[26]
Harborne, J.B.; Williams, C.A. Advances in flavonoid research since 1992. Phytochemistry, 2000, 55(6), 481-504.
[27]
Cho, H.; Yun, C.W.; Park, W.K.; Kong, J.Y.; Kim, K.S.; Park, Y.; Lee, B.; Kim, B.K. Modulation of the activity of pro-inflammatory enzymes, COX-2 and iNOS, by chrysin derivatives. Pharmacol. Res., 2004, 49(1), 37-43.
[28]
Liang, Y.C.; Tsai, S.H.; Tsai, D.C.; Lin-Shiau, S.Y.; Lin, J.K. Suppression of inducible cyclooxygenase and nitric oxide synthase through activation of peroxisome proliferators-activated receptor-γ by flavonoids in mouse macrophages. FEBS Lett., 2001, 496(1), 12-18.
[29]
Wadibhasme, P.G.; Ghaisas, M.M.; Thakurdesai, P.A. Anti-asthmatic potential of chrysin on ovalbumin-induced bronchoalveolar hyperresponsiveness in rats. Pharm. Biol., 2011, 49(5), 508-515.
[30]
Testai, L.; Martelli, A.; Cristofaro, M.; Breschi, M.C.; Calderone, V. Cardioprotective effects of different flavonoids against myocardial ischaemia/reperfusion injury in Langendorff-perfused rat hearts. J. Pharm. Pharmacol., 2013, 65(5), 750-756.
[31]
Tian, S.S.; Jiang, F.S.; Zhang, K.; Zhu, X.X.; Jin, B.; Lu, J.J.; Ding, Z.S. Flavonoids from the leaves of Carya cathayensis Sarg. inhibit vascular endothelial growth factor-induced angiogenesis. Fitoterapia, 2014, 92, 34-40.
[32]
Zeng, W.; Yan, Y.; Zhang, F.; Zhang, C.; Liang, W. Chrysin promotes osteogenic differentiation via ERK/MAPK activation. Protein Cell, 2013, 4(7), 539-547.
[33]
Whiting, D.R.; Guariguata, L.; Weil, C.; Shaw, J. IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res. Clin. Pract., 2011, 94(3), 311-321.
[34]
Ceriello, A. New insights on oxidative stress and diabetic complications may lead to a “causal” antioxidant therapy. Diabetes Care, 2003, 26(5), 1589-1596.
[35]
Shin, J.S.; Kim, K.S.; Kim, M.B.; Jeong, J.H.; Kim, B.K. Synthesis and hypoglycemic effect of chrysin derivatives. Bioorg. Med. Chem. Lett., 1999, 9(6), 869-874.
[36]
Kröncke, K.D.; Fehsel, K.; Suschek, C.; Kolb-Bachofen, V. Inducible nitric oxide synthase-derived nitric oxide in gene regulation, cell death and cell survival. Int. Immunopharmacol., 2001, 1(8), 1407-1420.
[37]
Zou, X.Q.; Peng, S.M.; Hu, C.P.; Tan, L.F.; Yuan, Q.; Deng, H.W.; Li, Y.J. Synthesis, characterization and vasculoprotective effects of nitric oxide-donating derivatives of chrysin. Bioorg. Med. Chem., 2010, 18(9), 3020-3025.
[38]
Jaganathan, S.K.; Mandal, M. Antiproliferative effects of honey and of its polyphenols: A review. BioMed Res. Int., 2009, •••
[http://dx.doi.org/10.1155/2009/830616]
[39]
Sawicka, D.; Car, H.; Borawska, M.H.; Nikliński, J. The anticancer activity of propolis. Folia Histochem. Cytobiol., 2012, 50(1), 25-37.
[40]
Khoo, B.Y.; Chua, S.L.; Balaram, P. Apoptotic effects of chrysin in human cancer cell lines. Int. J. Mol. Sci., 2010, 11(5), 2188-2199.
[41]
Kelekar, A.; Chang, B.S.; Harlan, J.E.; Fesik, S.W.; Thompson, C.B. Bad is a BH3 domain-containing protein that forms an inactivating dimer with Bcl-XL. Mol. Cell. Biol., 1997, 17(12), 7040-7046.
[42]
Pelengaris, S.; Khan, M.; Gerard, E. c-MYC: More than just a matter of life and death. Nat. Rev. Cancer, 2002, 2(10), 764.
[43]
Debatin, K.M. Apoptosis pathways in cancer and cancer therapy. Cancer Immunol. Immunother., 2004, 53(3), 153-159.
[44]
Yoshida, K.; Hirose, Y.; Tanaka, T.; Yamada, Y.; Kuno, T.; Kohno, H.; Shibata, T. Inhibitory effects of troglitazone, a peroxisome proliferators-activated receptor γ ligand, in rat tongue carcinogenesis initiated with 4-nitroquinoline 1-oxide. Cancer Sci., 2003, 94(4), 365-371.
[45]
Woo, K.J.; Jeong, Y.J.; Park, J.W.; Kwon, T.K. Chrysin-induced apoptosis is mediated through caspase activation and akt inactivation in u937 leukemia cells. Biochem. Biophys. Res. Commun., 2004, 325(4), 1215-1222.
[46]
Ramos, A.M.; Aller, P. Quercetin decreases intracellular gsh content and potentiates the apoptotic action of the antileukemic drug arsenic trioxide in human leukemia cell lines. Biochem. Pharmacol., 2008, 75(10), 1912-1923.
[47]
Woo, K.J.; Yoo, Y.H.; Park, J.W.; Kwon, T.K. Bcl-2 attenuates anticancer agents-induced apoptosis by sustained activation of akt/protein kinase b in u937 cells. Apoptosis, 2005, 10(6), 1333-1343.
[48]
Paez, J.G.; Jänne, P.A.; Lee, J.C.; Tracy, S.; Greulich, H.; Gabriel, S.; Naoki, K. EGFR mutations in lung cancer: Correlation with clinical response to gefitinib therapy. Science, 2004, 304(5676), 1497-1500.
[49]
Lv, P.C.; Wang, K.R.; Li, Q.S.; Chen, J.; Sun, J.; Zhu, H.L. Design, synthesis and biological evaluation of chrysin long-chain derivatives as potential anticancer agents. Bioorg. Med. Chem., 2010, 18(3), 1117-1123.
[50]
Song, X.; Liu, Y.; Ma, J.; He, J.; Zheng, X.; Lei, X.; Jiang, G.; Zhang, L. Synthesis of novel amino acid derivatives containing chrysin as anti-tumor agents against human gastric carcinoma MGC-803 cells. Med. Chem. Res., 2015, 5(24), 1789-1798.
[51]
Liu, Y.; Song, X.; He, J.; Zheng, X.; Wu, H. Synthetic derivatives of chrysin and their biological activities. Med. Chem. Res., 2014, 23(2), 555-563.
[52]
Peng, S.M.; Zou, X.Q.; Ding, H.L.; Ding, Y.L.; Lin, Y.B. Synthesis and promotion angiogenesis effect of chrysin derivatives coupled to NO donors. Bioorg. Med. Chem. Lett., 2009, 19(4), 1264-1266.
[53]
Liu, H.; Liu, K.; Huang, Z.; Park, C.M.; Thimmegowda, N.R.; Jang, J.H. Ryoo, In-Ja.; Lee, K.W. A chrysin derivative suppresses skin cancer growth by inhibiting cyclin-dependent kinases. J. Biol. Chem., 2013, 288(36), 25924-25937.
[54]
Choi, S.; Oh, C.; Han, J.; Park, J.; Choi, J.H.; Min, N.Y.; Su, J.; Lee, D.H. Synthesis and biological evaluation of water-soluble organogermanium. Eur. J. Med. Chem., 2010, 45(4), 1654-1656.
[55]
Pi, J.; Zeng, J.; Luo, J.J.; Yang, P.H.; Cai, J.Y. Synthesis and biological evaluation of Germanium (IV)–polyphenol complexes as potential anti-cancer agents. Bioorg. Med. Chem. Lett., 2013, 23(10), 2902-2908.
[56]
Yang, F.; Jin, H.; Pi, J.; Jiang, J.H.; Liu, L.; Bai, H.H.; Cai, J.Y. Anti-tumor activity evaluation of novel chrysin–organogermanium (IV) complex in MCF-7 cells. Bioorg. Med. Chem. Lett., 2013, 23(20), 5544-5551.
[57]
Aso, H.; Suzuki, F.; Yamagucht, T.; Hayashi, Y.; Ebina, T.; Ishida, N. Induction of interferon and activation of NK cells and macrophages in mice by oral administration of Ge-132, an organic germanium compound. Microbiol. Immunol., 1985, 29(1), 65-74.
[58]
Nakamura, T.; Nagura, T.; Akiba, M.; Sato, K.; Tokuji, Y.; Ohnishi, M.; Osada, K. Promotive effects of the dietary organic germanium poly-trans-[(2-carboxyethyl) germasesquioxane](Ge-132) on the secretion and antioxidative activity of bile in rodents. J. Health Sci., 2010, 56(1), 72-80.
[59]
Yang, F.; Gong, L.; Jin, H.; Pi, J.; Bai, H.; Wang, H.; Wang, H.; Cai, H.; Yang, P.; Cai, J. Chrysin-organogermanium (IV) complex induced Colo205 cell apoptosis-associated mitochondrial function and anti‐angiogenesis. Scanning, 2015, 37(4), 246-257.
[60]
Tang, Q.; Ji, F.; Guo, J.; Wang, J.; Li, Y.; Bao, Y. Directional modification of chrysin for exerting apoptosis and enhancing significantly anti-cancer effects of 10-hydroxy camptothecin. Biomed. Pharmacother., 2016, 82, 693-703.
[61]
Zhu, Z.Y.; Wang, W.X.; Wang, Z.Q.; Chen, L.J.; Zhang, J.Y.; Liu, X.C.; Wu, S.; Zhang, Y.M. Synthesis and antitumor activity evaluation of chrysin derivatives. Eur. J. Med. Chem., 2014, 75, 297-300.
[62]
Zou, X.Q.; Peng, S.M.; Hu, C.P.; Tan, L.F.; Deng, H.W.; Li, Y.J. Furoxan nitric oxide donor coupled chrysin derivatives: Synthesis and vasculoprotection. Bioorg. Med. Chem. Lett., 2011, 21(4), 1222-1226.
[63]
Zhang, T.; Chen, X.; Qu, L.; Wu, J.; Cui, R.; Zhao, Y. Chrysin and its phosphate ester inhibit cell proliferation and induce apoptosis in Hela cells. Bioorg. Med. Chem., 2004, 12(23), 6097-6105.
[64]
Beirne, J.J.; Carroll, N.M.; O’Sullivan, W.I.; Woods, J. Alkylation of the chrysin dianion. Tetrahedron, 1975, 31(3), 265-267.
[65]
Zheng, X.; Meng, W.D.; Xu, Y.Y.; Cao, J.G.; Qing, F.L. Synthesis and anticancer effect of chrysin derivatives. Bioorg. Med. Chem. Lett., 2003, 13(5), 881-884.
[66]
Hu, K.; Wang, W.; Cheng, H.; Pan, S.; Ren, J. Synthesis and cytotoxicity of novel chrysin derivatives. Med. Chem. Res., 2011, 20(7), 838-846.
[67]
Bell, I.R.; Schwartz, G.E.; Boyer, N.N.; Koithan, M.; Brooks, A.J. Advances in integrative nanomedicine for improving infectious disease treatment in public health. Eur. J. Integr. Med., 2013, 5(2), 126-140.
[68]
Liang, Y.; Deng, X.; Zhang, L.; Peng, X.; Gao, W.; Cao, J.; Gu, Z.; He, B. Terminal modification of polymeric micelles with π-conjugated moieties for efficient anticancer drug delivery. Biomaterials, 2015, 71, 1-10.
[69]
Zheng, H.; Li, S.; Pu, Y.; Lai, Y.; He, B.; Gu, Z. Nanoparticles generated by PEG-Chrysin conjugates for efficient anticancer drug delivery. Eur. J. Pharm. Biopharm., 2014, 87(3), 454-460.
[70]
Anari, E.; Akbarzadeh, A.; Zarghami, N. Chrysin-loaded PLGA-PEG nanoparticles designed for enhanced effect on the breast cancer cell line. Artif. Cells Nanomed. Biotechnol., 2016, 44(6), 1410-1416.
[71]
Mohammadinejad, S.; Akbarzadeh, A.; Rahmati-Yamchi, M.; Hatam, S.; Kachalaki, S.; Zohreh, S.; Zarghami, N. Preparation and evaluation of chrysin encapsulated in PLGA-PEG nanoparticles in the T47-D breast cancer cell line. Asian Pac. J. Cancer Prev., 2015, 16(9), 3753-3758.
[72]
Cheng, F.R.; Yang, Y.J.; Liang, Y.; Yan, J.Q.; Cao, J.; Su, T.; He, B.; Luo, X.B.; Gu, Z.W.W. Correlation of polymeric micelle sizes and their cellular internalization in vitro and tumor targeting in vivo. RSC Advances, 2014, 4(107), 62708-62716.
[73]
Babu, K.S.; Babu, T.H.; Srinivas, P.V.; Kishore, K.H.; Murthy, U.S.N.; Rao, J.M. Synthesis and biological evaluation of novel C (7) modified chrysin analogues as antibacterial agents. Bioorg. Med. Chem. Lett., 2006, 16(1), 221-224.
[74]
Li, H.Q.; Shi, L.; Li, Q.S.; Liu, P.G.; Luo, Y.; Zhao, J.; Zhu, H.L. Synthesis of C (7) modified chrysin derivatives designing to inhibit β-ketoacyl-acyl carrier protein synthase III (FabH) as antibiotics. Bioorg. Med. Chem., 2009, 17(17), 6264-6269.
[75]
Puupponen-Pimiä, R.; Nohynek, L.; Meier, C.; Kähkönen, M.; Heinonen, M.; Hopia, A.; Oksman-Caldentey, K.M. Antimicrobial properties of phenolic compounds from berries. J. Appl. Microbiol., 2001, 90(4), 494-507.
[76]
Rendón-Nava, D.; Mendoza-Espinosa, D.; Negrón-Silva, G.E.; Téllez-Arreola, J.L.; Martínez-Torres, A.; Valdez-Calderón, A.; González-Montiel, S. Chrysin functionalized NHC-Au (i) complexes: synthesis, characterization and effects on the nematode Caenorhabditis elegans. J. Chem., 2017, 41(5), 2013-2019.
[77]
Ramesh, P.; Reddy, C.S.; Babu, K.S.; Reddy, P.M.; Rao, V.S.; Parthasarathy, T. Synthesis, characterization and molecular docking studies of novel 2-amino 3-cyano pyrano [2, 3H] chrysin derivatives as potential antimicrobial agents. Med. Chem. Res., 2015, 10(24), 3696-3709.
[78]
Park, H.; Dao, T.T.; Kim, H.P. Synthesis and inhibition of PGE 2 production of 6, 8-disubstituted chrysin derivatives. Eur. J. Med. Chem., 2005, 40(9), 943-948.
[79]
Dao, T.T.; Kim, S.B.; Sin, K.S.; Kim, S.; Kim, H.P.; Park, H. Synthesis and biological activities of 8-arylflavones. Arch. Pharm. Res., 2004, 27(3), 278-282.
[80]
Che, H.; Lim, H.; Kim, H.P.; Park, H. A chrysin analog exhibited strong inhibitory activities against both PGE 2 and NO production. Eur. J. Med. Chem., 2011, 46(9), 4657-4660.
[81]
Lim, H.; Jin, J.H.; Park, H.; Kim, H.P. New synthetic anti-inflammatory chrysin analog, 5, 7-dihydroxy-8-(pyridine-4yl) flavone. Eur. J. Pharmacol., 2011, 670(2), 617-622.
[82]
Singh, P.; Kaur, J.; Singh, G.; Bhatti, R. Triblock conjugates: identification of a highly potent antiinflammatory agent. J. Med. Chem., 2015, 58(15), 5989-6001.
[83]
Lv, P.C.; Cai, T.T.; Qian, Y.; Sun, J.; Zhu, H.L. Synthesis, biological evaluation of chrysin derivatives as potential immunosuppressive agents. Eur. J. Med. Chem., 2011, 46(1), 393-398.
[84]
Lv, P.C.; Cai, T.T.; Qian, Y.; Sun, J.; Zhu, H.L. Synthesis, biological evaluation of chrysin derivatives as potential immunosuppressive agents. Eur. J. Med. Chem., 2011, 46(1), 393-398.
[85]
Wang, J.; Zhang, T.; Du, J.; Cui, S.; Yang, F.; Jin, Q. Anti-enterovirus 71 effects of chrysin and its phosphate ester. PLoS One, 2014, 9(3), e89668.
[86]
Song, J.H.; Kwon, B.E.; Jang, H.; Kang, H.; Cho, S.; Park, K.; Ko, H.; Kim, H. Antiviral Activity of Chrysin Derivatives against Coxsackievirus B3 in vitro and in vivo. Biomol. Therapeut., 2015, 23(5), 465.
[87]
Kedika, B.; Noole, V.; Thotla, K.; Chepyala, K.R. Synthesis of chrysin based cationic lipids: Plasmid delivery and transgene expression.Applications of Process Engineering Principles in Materials Processing, Energy and Environmental Technologies; Springer International Publishing, 2017, pp. 373-381.
[88]
Dao, T.T.; Sook Chi, Y.; Kim, J.; Kim, H.P.; Kim, S.; Park, H. Synthesis and PGE 2 inhibitory activity of 5, 7-dihydroxyflavones and their O-methylated flavone analogs. Arch. Pharm. Res., 2003, 26(5), 345-350.
[89]
Zheng, X.; Zhao, F.F.; Liu, M. Y.; Yao, X.; Zheng, Z.T.; Luo, X.; Liao, D.F. Synthesis and preliminary biological evaluation of chrysin derivatives as potential anticancer drugs. Med. Chem., 2010, 6(1), 6-8.
[90]
Naso, L.; Ferrer, E.G.; Lezama, L.; Rojo, T.; Etcheverry, S.B.; Williams, P. Role of oxidative stress in the antitumoral action of a new vanadyl (IV) complex with the flavonoid chrysin in two osteoblast cell lines: Relationship with the radical scavenger activity. J. Biol. Inorg. Chem., 2010, 15(6), 889-902.
[91]
Naso, L.G.; Valcarcel, M.; Roura-Ferrer, M.; Kortazar, D.; Salado, C.; Lezama, L.; Rojo, T.; González-Baró, A.; Williams, P.; Ferrer, E.G. Promising antioxidant and anticancer (human breast cancer) oxidovanadium (IV) complex of chlorogenic acid. Synthesis, characterization and spectroscopic examination on the transport mechanism with bovine serum albumin. J. Inorg. Biochem., 2014, 135, 86-99.
[92]
Leon, I.E.; Di Virgilio, A.L.; Porro, V.; Muglia, C.I.; Naso, L.G.; Williams, P.A.M. BollatiFogolin, M.; Etcheverry, S.B. Antitumor properties of a vanadyl (IV) complex with the flavonoid chrysin [VO(chrysin)2EtOH]2 in a human osteosarcoma model: The role of oxidative stress and apoptosis. Dalton Trans., 2013, 42(33), 11868-11880.
[93]
Jacob, C.; Giles, G.I.; Giles, N.M.; Sies, H. Sulfur and selenium: The role of oxidation state in protein structure and function. Angew. Chem. Int. Ed., 2003, 42(39), 4742-4758.
[94]
Ravishankar, D.; Watson, K.A.; Greco, F.; Osborn, H.M. Novel synthesised flavone derivatives provide significant insight into the structural features required for enhanced anti-proliferative activity. RSC Advances, 2016, 6(69), 64544-64556.
[95]
Naithani, R. Organoselenium compounds in cancer chemoprevention. Mini Rev. Med. Chem., 2008, 8(7), 657-668.
[96]
Martins, I.L.; Charneira, C.; Gandin, V.; Ferreira da Silva, J.L.; Justino, G.C.; Telo, J.P.; Vieira, J.; Marzano, C.; Antunes, A.M. Selenium-containing chrysin and quercetin derivatives: Attractive scaffolds for cancer therapy. J. Med. Chem., 2015, 58(10), 4250-4265.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 19
ISSUE: 7
Year: 2019
Page: [555 - 568]
Pages: 14
DOI: 10.2174/1389557518666180424094821
Price: $58

Article Metrics

PDF: 33
HTML: 3
EPUB: 1
PRC: 1