Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Author(s): Sushmitha Jayaprakash, Sruthi Ramesh, Aishwarya Karthikeyan, Sivasubramanian Murugappan, Priyadharshini Sidharthan and Stalin Selvaraj*

DOI: 10.2174/1871520622666220520093018

DownloadDownload PDF Flyer Cite As
Transition Metal Coordination Complexes of Flavonoids: A Class of Better Pharmacological Active Molecules to Develop New Drugs

Page: [417 - 431] Pages: 15

  • * (Excluding Mailing and Handling)

Abstract

Flavonoid metal ion complexes are one of the classes of biologically active molecules with immense pharmacological potential, including antioxidant, antidiabetic, antimicrobial, and anticancer activity, to name a few. The effectiveness of this complexion depends on the state and nature of the transition metal ions and on the position to which the metal ion coordinates with their corresponding parent flavonoid. The metal coordination of flavonoids also improves the biological activities to a maximum extent compared to the parent compound. This may be attributed to many factors such as metal ions, coordination sites, structural configuration, and stability of the complexes. On the other hand, some of the metal ion complexes reduce the biological efficiency of the corresponding parent flavonoids, which can be due to the shift from antioxidant to pro-oxidant nature as well as the stability of the complexes both in in vitro and in vivo conditions. However, the literature on the stability of flavonoid metal ion complexes in in vivo conditions is very scanty. Therefore, this review summarizes and critically addresses all these parameters a favor together in a single slot that favours for the researchers to put forward to understand the mode and detailed molecular mechanism of flavonoid metals complexes compared with their corresponding parent flavonoids.

Keywords: Antioxidant, flavonoids, antidiabetic, biological activity, antimicrobial, metal complexes, anticancer, parent flavonoid.

Graphical Abstract

[1]
Havsteen, B.H. The biochemistry and medical significance of the flavonoids. Pharmacol. Ther., 2002, 96(2-3), 67-202.
[http://dx.doi.org/10.1016/S0163-7258(02)00298-X] [PMID: 12453566]
[2]
Kandaswami, C.; Lee, L.T.; Lee, P-P.H.; Hwang, J-J.; Ke, F-C.; Huang, Y-T.; Lee, M.T. The antitumor activities of flavonoids. in vivo. In Vivo, 2005, 19(5), 895-909.
[PMID: 16097445]
[3]
Pan, M-H.; Lai, C-S.; Ho, C-T. Anti-inflammatory activity of natural dietary flavonoids. Food Funct., 2010, 1(1), 15-31.
[http://dx.doi.org/10.1039/c0fo00103a] [PMID: 21776454]
[4]
Mokrzycki, K. Anti-atherosclerotic efficacy of quercetin and sodium phenylbutyrate in rabbits. Ann. Acad. Med. Stetin., 2000, 46, 189-200. Anti-atherosclerotic efficacy of quercetin and sodium phenylbutyrate in rabbits.
[PMID: 11712304]
[5]
Procházková, D.; Boušová, I.; Wilhelmová, N. Antioxidant and prooxidant properties of flavonoids. Fitoterapia, 2011, 82(4), 513-523.
[http://dx.doi.org/10.1016/j.fitote.2011.01.018] [PMID: 21277359]
[6]
Bansal, P.; Paul, P.; Mudgal, J.; Nayak, P.G.; Pannakal, S.T.; Priyadarsini, K.I.; Unnikrishnan, M.K. Antidiabetic, antihyperlipidemic and antioxidant effects of the flavonoid rich fraction of Pilea microphylla (L.) in high fat diet/streptozotocin-induced diabetes in mice. Exp. Toxicol. Pathol., 2012, 64(6), 651-658.
[http://dx.doi.org/10.1016/j.etp.2010.12.009] [PMID: 21208790]
[7]
Miyazawa, M.; Hisama, M. Antimutagenic activity of flavonoids from Chrysanthemum morifolium. Biosci. Biotechnol. Biochem., 2003, 67(10), 2091-2099.
[http://dx.doi.org/10.1271/bbb.67.2091] [PMID: 14586095]
[8]
Goto, S.; Handa, S. Antithrombotic effects of flavonoid. Circulation, 2001, 103(4), E23.
[http://dx.doi.org/10.1161/01.CIR.103.4.e23] [PMID: 11157735]
[9]
Duarte, J.; Pérez Vizcaíno, F.; Utrilla, P.; Jiménez, J.; Tamargo, J.; Zarzuelo, A. Vasodilatory effects of flavonoids in rat aortic smooth muscle. Structure-activity relationships. Gen. Pharmacol., 1993, 24(4), 857-862.
[http://dx.doi.org/10.1016/0306-3623(93)90159-U] [PMID: 8224739]
[10]
Wleklik, M.; Luczak, M.; Panasiak, W.; Kobus, M.; Lammer-Zarawska, E. Structural basis for antiviral activity of flavonoids-naturally occurring compounds. Acta Virol., 1988, 32(6), 522-525.
[PMID: 2906224]
[11]
Ohnishi, E.; Bannai, H. Quercetin potentiates TNF-induced antiviral activity. Antiviral Res., 1993, 22(4), 327-331.
[http://dx.doi.org/10.1016/0166-3542(93)90041-G] [PMID: 8279819]
[12]
Spencer, J.P.E. Flavonoids and brain health: Multiple effects underpinned by common mechanisms. Genes Nutr., 2009, 4(4), 243-250.
[http://dx.doi.org/10.1007/s12263-009-0136-3] [PMID: 19685255]
[13]
Mohan, A.; Narayanan, S.; Sethuraman, S.; Krishnan, U.M. Combinations of plant polyphenols & anti-cancer molecules: A novel treat-ment strategy for cancer chemotherapy. Anticancer. Agents Med. Chem., 2013, 13(2), 281-295.
[http://dx.doi.org/10.2174/1871520611313020015] [PMID: 22721388]
[14]
Ansari, A.; Sharma, R. Synthesis and characterization of a biologically active Lanthanum(III)Catechin complex and DNA binding spectro-scopic studies. Spectrosc. Lett., 2009, 42(4), 178-185.
[http://dx.doi.org/10.1080/00387010902827718]
[15]
Aherne, S.A.; O’Brien, N.M. Mechanism of protection by the flavonoids, quercetin and rutin, against tert-butylhydroperoxide- and mena-dione-induced DNA single strand breaks in Caco-2 cells. Free Radic. Biol. Med., 2000, 29(6), 507-514.
[http://dx.doi.org/10.1016/S0891-5849(00)00360-9] [PMID: 11025194]
[16]
Afanas’eva, I.B.; Ostrakhovitch, E.A.; Mikhal’chik, E.V.; Ibragimova, G.A.; Korkina, L.G. Enhancement of antioxidant and anti-inflammatory activities of bioflavonoid rutin by complexation with transition metals. Biochem. Pharmacol., 2001, 61(6), 677-684.
[http://dx.doi.org/10.1016/S0006-2952(01)00526-3] [PMID: 11266652]
[17]
Fernandez, M.T.; Mira, M.L.; Florêncio, M.H.; Jennings, K.R. Iron and copper chelation by flavonoids: An electrospray mass spectrome-try study. J. Inorg. Biochem., 2002, 92(2), 105-111.
[http://dx.doi.org/10.1016/S0162-0134(02)00511-1] [PMID: 12459155]
[18]
Mira, L.; Fernandez, M.T.; Santos, M.; Rocha, R.; Florêncio, M.H.; Jennings, K.R. Interactions of flavonoids with iron and copper ions: A mechanism for their antioxidant activity. Free Radic. Res., 2002, 36(11), 1199-1208.
[http://dx.doi.org/10.1080/1071576021000016463] [PMID: 12592672]
[19]
Payán-Gómez, S.A.; Flores-Holguín, N.; Pérez-Hernández, A.; Piñón-Miramontes, M.; Glossman-Mitnik, D. Computational molecular characterization of the flavonoid Morin and its Pt(II), Pd(II) and Zn(II) complexes. J. Mol. Model., 2011, 17(5), 979-985.
[http://dx.doi.org/10.1007/s00894-010-0789-2] [PMID: 20628776]
[20]
Svetlana, T.S.; Munteanu, M. Synthesis, characterization and antioxidant activity of cooper-quercetin complex and iron-quercetin com-plex. Revista de Chimie, 2018, 69(10), 2621-2624.
[http://dx.doi.org/10.37358/RC.18.10.6593]
[21]
Chen, W.; Sun, S.; Cao, W.; Liang, Y.; Song, J. Antioxidant property of quercetin–Cr(III) complex: The role of Cr(III) ion. J. Mol. Struct., 2009, 918(1-3), 194-197.
[http://dx.doi.org/10.1016/j.molstruc.2008.08.008]
[22]
Tripathy, D.R.; Roy, A.S.; Dasgupta, S. Complex formation of rutin and quercetin with copper alters the mode of inhibition of ribonucle-ase A. FEBS Lett., 2011, 585(20), 3270-3276.
[http://dx.doi.org/10.1016/j.febslet.2011.09.005] [PMID: 21924266]
[23]
Pękal, A.; Biesaga, M.; Pyrzynska, K. Interaction of quercetin with copper ions: Complexation, oxidation and reactivity towards radicals. Biometals, 2011, 24(1), 41-49.
[http://dx.doi.org/10.1007/s10534-010-9372-7] [PMID: 20835752]
[24]
Tan, J.; Wang, B.; Zhu, L. DNA binding and oxidative DNA damage induced by a quercetin copper(II) complex: Potential mechanism of its antitumor properties. Eur. J. Biochem., 2009, 14(5), 727-739.
[http://dx.doi.org/10.1007/s00775-009-0486-8] [PMID: 19259707]
[25]
Ni, Y.; Du, S.; Kokot, S. Interaction between quercetin-copper(II) complex and DNA with the use of the Neutral Red dye fluorophor probe. Anal. Chim. Acta, 2007, 584(1), 19-27.
[http://dx.doi.org/10.1016/j.aca.2006.11.006] [PMID: 17386580]
[26]
El Hajji, H.; Nkhili, E.; Tomao, V.; Dangles, O. Interactions of quercetin with iron and copper ions: Complexation and autoxidation. Free Radic. Res., 2006, 40(3), 303-320.
[http://dx.doi.org/10.1080/10715760500484351] [PMID: 16484047]
[27]
Dowling, S.; Regan, F.; Hughes, H. The characterisation of structural and antioxidant properties of isoflavone metal chelates. J. Inorg. Biochem., 2010, 104(10), 1091-1098.
[http://dx.doi.org/10.1016/j.jinorgbio.2010.06.007] [PMID: 20656356]
[28]
Ren, J.; Meng, S.; Lekka, ChE.; Kaxiras, E. Complexation of flavonoids with iron: Structure and optical signatures. J. Phys. Chem. B, 2008, 112(6), 1845-1850.
[http://dx.doi.org/10.1021/jp076881e] [PMID: 18211058]
[29]
Malešev, D.; Kuntić, V. Investigation of metal-flavonoid chelates and the determination of flavonoids via metal-flavonoid complexing reactions. J. Serb. Chem. Soc., 2007, 72(10), 921-939.
[http://dx.doi.org/10.2298/JSC0710921M]
[30]
Pereira, R.M.; Andrades, N.E.; Paulino, N.; Sawaya, A.C.; Eberlin, M.N.; Marcucci, M.C.; Favero, G.M.; Novak, E.M.; Bydlowski, S.P. Synthesis and characterization of a metal complex containing naringin and Cu, and its antioxidant, antimicrobial, antiinflammatory and tumor cell cytotoxicity. Molecules, 2007, 12(7), 1352-1366.
[http://dx.doi.org/10.3390/12071352] [PMID: 17909491]
[31]
Selvaraj, S.; Krishnaswamy, S.; Devashya, V.; Sethuraman, S.; Krishnan, U.M. Synthesis, characterization and DNA binding properties of rutin–iron complex. RSC Advances, 2012, 2(7), 2797-2802.
[http://dx.doi.org/10.1039/c2ra01319c]
[32]
Uivarosi, V.; Barbuceanu, S.F.; Aldea, V.; Arama, C-C.; Badea, M.; Olar, R.; Marinescu, D. Synthesis, spectral and thermal studies of new rutin vanadyl complexes. Molecules, 2010, 15(3), 1578-1589.
[http://dx.doi.org/10.3390/molecules15031578] [PMID: 20336002]
[33]
Selvaraj, S.; Krishnaswamy, S.; Devashya, V.; Sethuraman, S.; Krishnan, U.M. Membrane fluidization and eryptotic properties of hesperi-din–copper complex. RSC Advances, 2012, 2(29), 11138-11146.
[http://dx.doi.org/10.1039/c2ra20620j]
[34]
Etcheverry, S.B.; Ferrer, E.G.; Naso, L.; Rivadeneira, J.; Salinas, V.; Williams, P.A.M. Antioxidant effects of the VO(IV) hesperidin com-plex and its role in cancer chemoprevention. J. Biol. Inorg. Chem., 2008, 13(3), 435-447.
[http://dx.doi.org/10.1007/s00775-007-0332-9] [PMID: 18097692]
[35]
Kuntić, V.; Filipović, I.; Vujić, Z. Effects of rutin and hesperidin and their Al(III) and Cu(II) complexes on in vitro plasma coagulation assays. Molecules, 2011, 16(2), 1378-1388.
[http://dx.doi.org/10.3390/molecules16021378] [PMID: 21301410]
[36]
Tan, M.; Zhu, J.; Pan, Y.; Chen, Z.; Liang, H.; Liu, H.; Wang, H. Synthesis, cytotoxic activity, and DNA binding properties of copper (II) complexes with hesperetin, naringenin, and apigenin. Bioinorg. Chem. Appl., 2009, 2009, 347872-347872.
[http://dx.doi.org/10.1155/2009/347872] [PMID: 19830248]
[37]
McCord, J.M.; Fridovich, I. Superoxide dismutase: The first twenty years (1968-1988). Free Radic. Biol. Med., 1988, 5(5-6), 363-369.
[http://dx.doi.org/10.1016/0891-5849(88)90109-8] [PMID: 2855736]
[38]
Suksrichavalit, T.; Prachayasittikul, S.; Piacham, T.; Isarankura-Na-Ayudhya, C.; Nantasenamat, C.; Prachayasittikul, V. Copper complex-es of nicotinic-aromatic carboxylic acids as superoxide dismutase mimetics. Molecules, 2008, 13(12), 3040-3056.
[http://dx.doi.org/10.3390/molecules13123040] [PMID: 19078847]
[39]
Bukhari, S.B.; Memon, S.; Mahroof-Tahir, M.; Bhanger, M.I. Synthesis, characterization and antioxidant activity copper-quercetin com-plex. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2009, 71(5), 1901-1906.
[http://dx.doi.org/10.1016/j.saa.2008.07.030] [PMID: 18783981]
[40]
Kostyuk, V.; Potapovitch, A.; Kostyuk, T.; Cherian, G. Metal complexes of dietary flavonoids: Evaluation of radical scavenger properties and protective activity against oxidative stress in vivo. Cell. Mol. Biol., 2007, 53, 62-69.
[41]
Gopalakrishnan, V.; Iyyam Pillai, S.; Subramanian, S.P. Synthesis, spectral characterization, and biochemical evaluation of antidiabetic properties of a new zinc-diosmin complex studied in high fat diet fed-low dose streptozotocin induced experimental type 2 diabetes in rats. Biochem. Res. Int., 2015, 2015, 350829-350829.
[http://dx.doi.org/10.1155/2015/350829] [PMID: 26783461]
[42]
Dong, H.; Yang, X.; He, J.; Cai, S.; Xiao, K.; Zhu, L. Enhanced antioxidant activity, antibacterial activity and hypoglycemic effect of luteo-lin by complexation with manganese(ii) and its inhibition kinetics on xanthine oxidase. RSC Advances, 2017, 7(84), 53385-53395.
[http://dx.doi.org/10.1039/C7RA11036G]
[43]
Uivarosi, V.; Badea, M.; Rodica, O.; Velescu, B.; Aldea, V. Synthesis and characterization of a new complex of oxovanadium (IV) with naringenin, as potential insulinomimetic agent. Farmacia, 2016, 64, 175-180.
[44]
Panhwar, Q.K.; Memon, S. Synthesis, characterization and antioxidant activity of rutin complexes. Pak. J. Anal. Environ. Chem., 2014, 15(2), 60-70.
[45]
Bravo, A.; Anacona, J.R. Metal complexes of the flavonoid quercetin: Antibacterial properties. Trans. Met. Chem. (Weinh.), 2001, 26(1), 20-23.
[http://dx.doi.org/10.1023/A:1007128325639]
[46]
Hirai, I.; Okuno, M.; Katsuma, R.; Arita, N.; Tachibana, M.; Yamamoto, Y. Characterisation of anti-Staphylococcus aureus activity of quercetin. Int. J. Food Sci. Technol., 2010, 45(6), 1250-1254.
[http://dx.doi.org/10.1111/j.1365-2621.2010.02267.x]
[47]
Cushnie, T.P.T.; Lamb, A.J. Antimicrobial activity of flavonoids. Int. J. Antimicrob. Agents, 2005, 26(5), 343-356.
[http://dx.doi.org/10.1016/j.ijantimicag.2005.09.002] [PMID: 16323269]
[48]
Kopacz, M.; Woźnicka, E.; Gruszecka, J. Antibacterial activity of morin and its complexes with La(III), Gd(III) and Lu(III) ions. Acta Pol. Pharm., 2005, 62(1), 65-67.
[PMID: 16022496]
[49]
Raza, A.; Xu, X.; Xia, L.; Xia, C.; Tang, J.; Ouyang, Z. Quercetin-iron complex: Synthesis, characterization, antioxidant, DNA binding, DNA cleavage, and antibacterial activity studies. J. Fluoresc., 2016, 26(6), 2023-2031.
[http://dx.doi.org/10.1007/s10895-016-1896-y] [PMID: 27481501]
[50]
Ramesh, P.; Rao, V.; Reddy, P.; Babu, K.; Mutheneni, S.R. Synthesis, biological evaluation and molecular modeling studies of novel C (7) modified analogues of chrysin. Lett. Drug Des. Discov., 2019, 16, 873-883.
[51]
Barnham, K.J.; Masters, C.L.; Bush, A.I. Neurodegenerative diseases and oxidative stress. Nat. Rev. Drug Discov., 2004, 3(3), 205-214.
[http://dx.doi.org/10.1038/nrd1330] [PMID: 15031734]
[52]
Lü, J-M.; Lin, P.H.; Yao, Q.; Chen, C. Chemical and molecular mechanisms of antioxidants: Experimental approaches and model systems. J. Cell. Mol. Med., 2010, 14(4), 840-860.
[http://dx.doi.org/10.1111/j.1582-4934.2009.00897.x] [PMID: 19754673]
[53]
Catarzi, S.; Romagnoli, C.; Marcucci, G.; Favilli, F.; Iantomasi, T.; Vincenzini, M.T. Redox regulation of ERK1/2 activation induced by sphingosine 1-phosphate in fibroblasts: Involvement of NADPH oxidase and platelet-derived growth factor receptor. Biochim. Biophys. Acta, 2011, 1810(4), 446-456.
[http://dx.doi.org/10.1016/j.bbagen.2011.01.005] [PMID: 21256191]
[54]
Anissi, J.; El Hassouni, M.; Ouardaoui, A.; Sendide, K. A comparative study of the antioxidant scavenging activity of green tea, black tea and coffee extracts: A kinetic approach. Food Chem., 2014, 150, 438-447.
[http://dx.doi.org/10.1016/j.foodchem.2013.11.009] [PMID: 24360473]
[55]
Cherrak, S.A.; Mokhtari-Soulimane, N.; Berroukeche, F.; Bensenane, B.; Cherbonnel, A.; Merzouk, H.; Elhabiri, M. In vitro antioxidant versus metal ion chelating properties of flavonoids: A structure-activity investigation. PLoS One, 2016, 11(10), e0165575-e0165575.
[http://dx.doi.org/10.1371/journal.pone.0165575] [PMID: 27788249]
[56]
Choi, E.J. Hesperetin induced G1-phase cell cycle arrest in human breast cancer MCF-7 cells: Involvement of CDK4 and p21. Nutr. Cancer, 2007, 59(1), 115-119.
[http://dx.doi.org/10.1080/01635580701419030] [PMID: 17927510]
[57]
Bratu, M.; Birghila, S.; Miresan, H.; Negreanu-Pirol, T.; Prajitura, C.; Calinescu, M. Biological activities of Zn(II) and Cu(II) complexes with quercetin and rutin: Antioxidant properties and UV-protection capacity. Revista de Chimie, 2014, 65, 544-549.
[58]
Islas, M.S.; Naso, L.G.; Lezama, L.; Valcarcel, M.; Salado, C.; Roura-Ferrer, M.; Ferrer, E.G.; Williams, P.A.M. Insights into the mecha-nisms underlying the antitumor activity of an oxidovanadium(IV) compound with the antioxidant naringenin. Albumin binding studies. J. Inorg. Biochem., 2015, 149, 12-24.
[http://dx.doi.org/10.1016/j.jinorgbio.2015.04.011] [PMID: 25957189]
[59]
Martínez Medina, J.J.; Naso, L.G.; Pérez, A.L.; Rizzi, A.; Okulik, N.B.; Ferrer, E.G.; Williams, P.A.M. Apigenin oxidovanadium(IV) cation interactions. Synthesis, spectral, bovine serum albumin binding, antioxidant and anticancer studies. J. Photochem. Photobiol. Chem., 2017, 344, 84-100.
[http://dx.doi.org/10.1016/j.jphotochem.2017.05.007]
[60]
Roy, S.; Mallick, S.; Chakraborty, T.; Ghosh, N.; Singh, A.K.; Manna, S.; Majumdar, S. Synthesis, characterisation and antioxidant activity of luteolin-vanadium(II) complex. Food Chem., 2015, 173, 1172-1178.
[http://dx.doi.org/10.1016/j.foodchem.2014.10.141] [PMID: 25466140]
[61]
Ghosh, N.; Chakraborty, T.; Mallick, S.; Mana, S.; Singha, D.; Ghosh, B.; Roy, S. Synthesis, characterization and study of antioxidant activity of quercetin-magnesium complex. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2015, 151, 807-813.
[http://dx.doi.org/10.1016/j.saa.2015.07.050] [PMID: 26172468]
[62]
Zhail, G-y.; Qu, W.; Yan, Z.; Zhu, W.; Duan, Y.; Wang, J. Synthesis, spectral and antioxidant properties of Tin(II)-rutin complex. Chem. Nat. Compd., 2014, 50(4), 624-628.
[http://dx.doi.org/10.1007/s10600-014-1039-0]
[63]
Panhwar, D.; Memon, S. Synthesis, spectral characterization and antioxidant activity of Tin(II)-morin complex. Pak. J. Anal. Environ., 2012, 13, 159-168.
[64]
Kostyuk, V.A.; Potapovich, A.I.; Strigunova, E.N.; Kostyuk, T.V.; Afanas’ev, I.B. Experimental evidence that flavonoid metal complexes may act as mimics of superoxide dismutase. Arch. Biochem. Biophys., 2004, 428(2), 204-208.
[http://dx.doi.org/10.1016/j.abb.2004.06.008] [PMID: 15246878]
[65]
de Souza, R.F.V.; De Giovani, W.F. Antioxidant properties of complexes of flavonoids with metal ions. Redox Rep., 2004, 9(2), 97-104.
[http://dx.doi.org/10.1179/135100004225003897] [PMID: 15231064]
[66]
Sungur, S.; Uzar, A. Investigation of complexes tannic acid and myricetin with Fe(III). Spectrochim. Acta A Mol. Biomol. Spectrosc., 2008, 69(1), 225-229.
[http://dx.doi.org/10.1016/j.saa.2007.03.038] [PMID: 17493867]
[67]
Uttara, B.; Singh, A.V.; Zamboni, P.; Mahajan, R.T. Oxidative stress and neurodegenerative diseases: A review of upstream and down-stream antioxidant therapeutic options. Curr. Neuropharmacol., 2009, 7(1), 65-74.
[http://dx.doi.org/10.2174/157015909787602823] [PMID: 19721819]
[68]
Brown, J.E.; Khodr, H.; Hider, R.C.; Rice-Evans, C.A. Rice-Evans, structural dependence of flavonoid interactions with Cu2+ ions: Impli-cations for their antioxidant properties. Biochem. J., 1998, 330(Pt 3), 1173-1178.
[69]
Liu, Y.; He, X.; Zuo, H.; Zhang, Q.; Li, Z.; Shi, L. Advance of studies on bioactivity of flavonoid-metal complexes. Zhongguo Zhongyao Zazhi, 2012, 37(13), 1901-1904.
[PMID: 23019867]
[70]
Yu, Y.; Lan, Y.M.; Wen, C.S. Study on synthesis and scavenging radical activity of complex Chromium(III)-quercetin. Shipin Kexue, 2006, 27, 29-32.
[71]
Shalini, V.; Bhaskar, S.; Kumar, K.S.; Mohanlal, S.; Jayalekshmy, A.; Helen, A. Molecular mechanisms of anti-inflammatory action of the flavonoid, tricin from Njavara rice (Oryza sativa L.) in human peripheral blood mononuclear cells: Possible role in the inflammatory sig-naling. Int. Immunopharmacol., 2012, 14(1), 32-38.
[http://dx.doi.org/10.1016/j.intimp.2012.06.005] [PMID: 22705359]
[72]
da S Emim. J.A.; Souccar, C.; de A Castro, M.S.; Godinho, R.O.; Cezari, M.H.; Juliano, L.; Lapa, A.J. Evidence for activation of the tissue kallikrein-kinin system in nociceptive transmission and inflammatory responses of mice using a specific enzyme inhibitor. Br. J. Pharmacol., 2000, 130(5), 1099-1107.
[http://dx.doi.org/10.1038/sj.bjp.0703362] [PMID: 10882395]
[73]
Middleton, E., Jr; Kandaswami, C.; Theoharides, T.C. The effects of plant flavonoids on mammalian cells: Implications for inflammation, heart disease, and cancer. Pharmacol. Rev., 2000, 52(4), 673-751.
[PMID: 11121513]
[74]
Li, J.; Wang, L.; Bai, H.; Yang, B.; Yang, H. Synthesis, characterization, and anti-inflammatory activities of rare earth metal complexes of luteolin. Med. Chem. Res., 2011, 20(1), 88-92.
[http://dx.doi.org/10.1007/s00044-009-9289-2]
[75]
Tan, J.; Wang, B.; Zhu, L. DNA binding, cytotoxicity, apoptotic inducing activity, and molecular modeling study of quercetin zinc(II) complex. Bioorg. Med. Chem., 2009, 17(2), 614-620.
[http://dx.doi.org/10.1016/j.bmc.2008.11.063] [PMID: 19097913]
[76]
Jun, T.; Bochu, W.; Liancai, Z. Hydrolytic cleavage of DNA by quercetin manganese(II) complexes. Colloids Surf. B Biointerfaces, 2007, 55(2), 149-152.
[http://dx.doi.org/10.1016/j.colsurfb.2006.11.044] [PMID: 17234390]
[77]
Roy, A.S.; Tripathy, D.R.; Samanta, S.; Ghosh, S.K.; Dasgupta, S. DNA damaging, cell cytotoxicity and serum albumin binding efficacy of the rutin-Cu(ii) complex. Mol. Biosyst., 2016, 12(5), 1687-1701.
[http://dx.doi.org/10.1039/C6MB00161K] [PMID: 27035097]
[78]
Wang, Q.; Huang, M.; Huang, Y.; Zhang, J-S.; Zhou, G-F.; Zeng, R.; Yang, X-B. Synthesis, characterization, DNA interaction, and anti-tumor activities of mixed-ligand metal complexes of kaempferol and 1,10-phenanthroline/2,R2-bipyridine. Med. Chem. Res., 2013, 23(5), 2659-2666.
[http://dx.doi.org/10.1007/s00044-013-0863-2]
[79]
Thangavel, P.; Viswanath, B.; Kim, S. Synthesis and characterization of kaempferol-based ruthenium (II) complex: A facile approach for superior anticancer application. Mater. Sci. Eng. C, 2018, 89, 87-94.
[http://dx.doi.org/10.1016/j.msec.2018.03.020] [PMID: 29752123]
[80]
Wang, Q.; Huang, Y.; Zhang, J-S.; Yang, X-B. Synthesis, characterization, DNA interaction, and antitumor activities of La (III) complex with schiff base ligand derived from kaempferol and diethylenetriamine. Bioinorg. Chem. Appl., 2014, 2014, 354138.
[http://dx.doi.org/10.1155/2014/354138] [PMID: 25371657]
[81]
Naso, L.G.; Lezama, L.; Valcárcel, M.; Salado, C.; Villacé, P.; Kortazar, D.; Ferrer, E.G.; Williams, P.A. Bovine serum albumin binding, antioxidant and anticancer properties of an oxidovanadium(IV) complex with luteolin. J. Inorg. Biochem., 2016, 157, 80-93.
[http://dx.doi.org/10.1016/j.jinorgbio.2016.01.021] [PMID: 26828287]
[82]
Naso, L.; Martínez, V.R.; Lezama, L.; Salado, C.; Valcárcel, M.; Ferrer, E.G.; Williams, P.A.M. Antioxidant, anticancer activities and mechanistic studies of the flavone glycoside diosmin and its oxidovanadium(IV) complex. Interactions with bovine serum albumin. Bioorg. Med. Chem., 2016, 24(18), 4108-4119.
[http://dx.doi.org/10.1016/j.bmc.2016.06.053] [PMID: 27374881]
[83]
Tamayo, L.V.; Gouvea, L.R.; Sousa, A.C.; Albuquerque, R.M.; Teixeira, S.F.; de Azevedo, R.A.; Louro, S.R.W.; Ferreira, A.K.; Beraldo, H. Copper(II) complexes with naringenin and hesperetin: Cytotoxic activity against A 549 human lung adenocarcinoma cells and investi-gation on the mode of action. Biometals, 2016, 29(1), 39-52.
[http://dx.doi.org/10.1007/s10534-015-9894-0] [PMID: 26582127]
[84]
Fazary, A.; Ju, Y-H.; Al-Shihri, A.; Bani-Fwaz, M.Z.; Alfaifi, M.; Alshehri, M.; Saleh, K.; Fawy, K.; Abd-Rabboh, H. Platinum and vana-date bioactive complexes of glycoside naringin and phenolates. Open Chem., 2017, 15(1), 15.
[http://dx.doi.org/10.1515/chem-2017-0022]
[85]
Atta, E.M.; Hegab, K.H.; Abdelgawad, A.A.M.; Youssef, A.A. Synthesis, characterization and cytotoxic activity of naturally isolated nar-ingin-metal complexes. Saudi Pharm. J., 2019, 27(4), 584-592.
[http://dx.doi.org/10.1016/j.jsps.2019.02.006] [PMID: 31061628]
[86]
Alper, P.; Erkisa, M.; Mutlu Gençkal, H.; Şahin, S.; Ulukaya, E.; Ari, F. Synthesis, characterization, anticancer and antioxidant activity of new nickel(II) and copper(II) flavonoid complexes. J. Mol. Struct., 2019, 1196, 1196.
[http://dx.doi.org/10.1016/j.molstruc.2019.07.009]
[87]
León, I.E.; Díez, P.; Etcheverry, S.B.; Fuentes, M. Deciphering the effect of an oxovanadium(iv) complex with the flavonoid chrysin (VOChrys) on intracellular cell signalling pathways in an osteosarcoma cell line. Metallomics, 2016, 8(8), 739-749.
[http://dx.doi.org/10.1039/C6MT00045B] [PMID: 27175625]
[88]
Durgo, K.; Halec, I.; Sola, I.; Franekić, J. Cytotoxic and genotoxic effects of the quercetin/lanthanum complex on human cervical carcino-ma cells in vitro. Arh. Hig. Rada Toksikol., 2011, 62(3), 221-227.
[http://dx.doi.org/10.2478/10004-1254-62-2011-2122] [PMID: 21971105]
[89]
Luana, M.; Chiara La, T.; Emilia, F.; Alessia, F.; Maria Cristina, C.; Erika, C.; Luca, G.; Tiziana, M.; Pierluigi, P. Aluminum(III), iron(III) and copper(II) complexes of luteolin: Stability, antioxidant, and anti-inflammatory properties. J. Mol. Liq., 2022, 345, 117895.
[http://dx.doi.org/10.1016/j.molliq.2021.117895]
[90]
Naso, L.G.; Martínez Medina, J.J.; Okulik, N.B.; Ferrer, E.G.; Williams, P.A.M.; Patricia, A.M. Study on the cytotoxic, antimetastatic and albumin binding properties of the oxidovanadium(IV) chrysin complex. Structural elucidation by computational methodologies. Chem. Biol. Interact., 2022, 351(5), 109750.
[http://dx.doi.org/10.1016/j.cbi.2021.109750] [PMID: 34813780]