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Current Pharmaceutical Design

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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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General Review Article

Potent Cytotoxic Natural Flavonoids: The Limits of Perspective

Author(s): Akram Taleghani and Zahra Tayarani-Najaran*

Volume 24, Issue 46, 2018

Page: [5555 - 5579] Pages: 25

DOI: 10.2174/1381612825666190222142537

Price: $65

Abstract

Background: Besides the numerous biologic and pharmacologic functions in the human body that act as potent antioxidants, flavonoids (flavones, flavanones, flavonols, flavanols and isoflavones) are noted as cancer preventive or therapeutic agents.

Methods: This review summarizes the published data using PubMed, Science Direct, and Scopus.

Results: In this context, recognition and introduction of the most active cytotoxic flavonoids as promising agents for cancer therapy gives insight for further evaluations. However, there are some critical points that may affect the entering of flavonoids as active cytotoxic phytochemicals in the clinical phase. Issues such as the abundance of active species in nature, the methods of extraction and purification, solubility, pharmacokinetic profile, presence of the chiral moieties, method of synthesis, and structure modification may limit the entry of a selected compound for use in humans. Although plenty of basic evidence exists for cytotoxic/antitumor activity of the versatility of flavonoids for entry into clinical trials, the above-mentioned concerns must be considered.

Conclusion: This review is an effort to introduce cytotoxic natural flavonoids (IC50< 10 µM) that may have the potential to be used against various tumor cells. Also, active constituents, molecular mechanisms, and related clinical trials have been discussed as well as the limitations and challenges of using flavonoids in clinic.

Keywords: Flavonoids, potent cytotoxic, molecular mechanism, clinical trial, limitations, potent antioxidants.

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[1]
Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010; 127: 2893-917.
[2]
Mousavi SM, Gouya MM, Ramazani R, Davanlou M, Hajsadeghi N, Seddighi Z. Cancer incidence and mortality in Iran. Ann Oncol 2008; 20: 556-63.
[3]
Newman DJ, Cragg GM. Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod 2012; 75: 311-35.
[4]
Pandey AK. Anti-staphylococcal activity of a pan-tropical aggressive and obnoxious weed Parthenium histerophorus: an in vitro study. Natl Acad Sci Lett 2007; 30: 383.
[5]
Cook N, Samman S. Flavonoids—chemistry, metabolism, cardioprotective effects, and dietary sources. J Nutr Biochem 1996; 7: 66-76.
[6]
Rice-evans CA, Miller NJ, Bolwell PG, Bramley PM, Pridham JB. The relative antioxidant activities of plant-derived polyphenolic flavonoids. Free Radic Res 1995; 22: 375-83.
[7]
Zhao Y, Zhao K, Jiang K, et al. A review of flavonoids from Cassia species and their biological activity. Curr Pharm Biotechnol 2016; 17: 1134-46.
[8]
Mahomoodally MF, Gurib-Fakim A, Subratty AH. Antimicrobial activities and phytochemical profiles of endemic medicinal plants of Mauritius. Pharm Biol 2005; 43: 237-42.
[9]
Boozari M, Mohammadi A, Asili J, Emami SA, Tayarani-Najaran Z. Growth inhibition and apoptosis induction by Scutellaria pinnatifida A. Ham. on HL-60 and K562 leukemic cell lines. Environ Toxicol Pharmacol 2015; 39: 307-12.
[10]
Tayarani-Najarani Z, Asili J, Parsaee H, et al. Wogonin and neobaicalein from Scutellaria litwinowii roots are apoptotic for HeLa cells. Rev Bras Farmacogn 2012; 22: 268-76.
[11]
Middleton E. Effect of plant flavonoids on immune and inflammatory cell function Flavonoids in the living system. Springer 1998; pp. 175-82.
[12]
Hollman P, Katan M. Absorption, metabolism and health effects of dietary flavonoids in man. Biomed Pharmacother 1997; 51: 305-10.
[13]
Yao LH, Jiang Y, Shi J, et al. Flavonoids in food and their health benefits. Plant Foods Hum Nutr 2004; 59: 113-22.
[14]
Eghbali Feriz S, Taleghani A, Tayarani-Najaran Z. Scutellaria: Debates on the anticancer property. Biomed Pharmacother 2018; 105: 1299-310.
[15]
Harborne JB, Williams CA. Advances in flavonoid research since 1992. Phytochemistry 2000; 55: 481-504.
[16]
Passreiter CM, Suckow-Schnitker A-K, Kulawik A, Addae-Kyereme J, Wright CW, Wätjen W. Prenylated flavanone derivatives isolated from Erythrina addisoniae are potent inducers of apoptotic cell death. Phytochemistry 2015; 117: 237-44.
[17]
Tchokouaha RF, Alexi X, Chosson E, et al. Erymildbraedin A and B, two novel cytotoxic dimethylpyrano-isoflavones from the stem bark of Erythrina mildbraedii: evaluation of their activity toward endocrine cancer cells. J Enzyme Inhib Med Chem 2010; 25: 228-33.
[18]
Innok P, Rukachaisirikul T, Suksamrarn A. Flavanoids and pterocarpans from the bark of Erythrina fusca. Chem Pharm Bull 2009; 57: 993-6.
[19]
Watjen W, Suckow-Schnitker A, Rohrig R, et al. Prenylated flavonoid derivatives from the bark of Erythrina addisoniae. J Nat Prod 2008; 71: 735-8.
[20]
Nkengfack AE, Azebaze AG, Waffo AK, Fomum ZT, Meyer M, van Heerden FR. Cytotoxic isoflavones from Erythrina indica. Phytochemistry 2001; 58: 1113-20.
[21]
Nguyen PH, Sharma G, Dao TT, et al. New prenylated isoflavonoids as protein tyrosine phosphatase 1B (PTP1B) inhibitors from Erythrina addisoniae. Bioorg Med Chem 2012; 20: 6459-64.
[22]
Ogunlana OO, He W-J, Fan J-T, et al. Cytotoxic flavonoids from the young twigs and leaves of Caesalpinia bonduc (Linn) Roxb. J Pharm Sci 2015; 28: 2191-8.
[23]
Rao YK, Geethangili M, Fang S-H, Tzeng Y-M. Antioxidant and cytotoxic activities of naturally occurring phenolic and related compounds: a comparative study. Food Chem Toxicol 2007; 45: 1770-6.
[24]
López-Lázaro M, Martín-Cordero C, Cortés F, Piñero J, Ayuso MJ. Cytotoxic activity of flavonoids and extracts from Retama sphaerocarpa Boissier. Z Naturforsch C 2000; 55: 40-3.
[25]
Svasti J, Srisomsap C, Subhasitanont P, et al. Proteomic profiling of cholangiocarcinoma cell line treated with pomiferin from Derris malaccensis. Proteomics 2005; 5: 4504-9.
[26]
Decharchoochart P, Suthiwong J, Samatiwat P, Kukongviriyapan V, Yenjai C. Cytotoxicity of compounds from the fruits of Derris indica against cholangiocarcinoma and HepG2 cell lines. J Nat Med 2014; 68: 730-6.
[27]
Shour S, Iranshahy M, Pham N, Quinn RJ, Iranshahi M. Dereplication of cytotoxic compounds from different parts of Sophora pachycarpa using an integrated method of HPLC, LC-MS and 1H-NMR techniques. Nat Prod Res 2017; 31: 1270-6.
[28]
Adem FA, Kuete V, Mbaveng AT, et al. Cytotoxic flavonoids from two Lonchocarpus species. Nat Prod Res 2018; 1-9.
[29]
Blatt CT, Chávez D, Chai H, et al. Cytotoxic flavonoids from the stem bark of Lonchocarpus aff. fluvialis. Phytother Res 2002; 16: 320-5.
[30]
Song S, Zheng X, Liu W, Du R, Bi L, Zhang P. 3-Hydroxymethylglutaryl flavonol glycosides from a Mongolian and Tibetan medicine, Oxytropis racemosa. Chem Pharm Bull 2010; 58: 1587-90.
[31]
Li X, Wang D, Xia M-y, Wang Z-h, Wang W-n, Cui Z. Cytotoxic prenylated flavonoids from the stem bark of Maackia amurensis. Chem Pharm Bull 2009; 57: 302-6.
[32]
Wu X, Liao H-B, Li G-Q, et al. Cytotoxic rotenoid glycosides from the seeds of Amorpha fruticosa. Fitoterapia 2015; 100: 75-80.
[33]
Song P, Yang X-Z, Yuan J-Q. Cytotoxic constituents from Psoralea corylifolia. J Asian Nat Prod Res 2013; 15: 624-30.
[34]
Haggag EG, Kamal AM, Abdelhady MI, El-Sayed MM, El-Wakil EA, Abd-El-hamed SS. Antioxidant and cytotoxic activity of polyphenolic compounds isolated from the leaves of Leucenia leucocephala. Pharm Biol 2011; 49: 1103-13.
[35]
Shults EE, Shakirov MM, Pokrovsky MA, Petrova TN, Pokrovsky AG, Gorovoy PG. Phenolic compounds from Glycyrrhiza pallidiflora Maxim. and their cytotoxic activity. Nat Prod Res 2017; 31: 445-52.
[36]
Mai HDT, Nguyen TTO, Pham VC, Litaudon M, Guéritte F, Tran DT. Cytotoxic prenylated isoflavone and bipterocarpan from Millettia pachyloba. Planta Med 2010; 76: 1739-42.
[37]
Sutthivaiyakit S, Thongnak O, Lhinhatrakool T, et al. Cytotoxic and antimycobacterial prenylated flavonoids from the roots of Eriosema chinense. J Nat Prod 2009; 72: 1092-6.
[38]
Joycharat N, Boonma C, Thammavong S, Yingyongnarongkul B-e, Limsuwan S, Voravuthikunchai SP. Chemical constituents and biological activities of Albizia myriophylla wood. Pharm Biol 2016; 54: 62-73.
[39]
Falcao MJC, Pouliquem YBM, Lima MAS, et al. Cytotoxic flavonoids from Platymiscium floribundum. J Nat Prod 2005; 68: 423-6.
[40]
Yokosuka A, Haraguchi M, Usui T, et al. Glaziovianin A, a new isoflavone, from the leaves of Ateleia glazioviana and its cytotoxic activity against human cancer cells. Bioorg Med Chem Lett 2007; 17: 3091-4.
[41]
Ren Y, Kardono LB, Riswan S, et al. Cytotoxic and NF-κB inhibitory constituents of Artocarpus rigida. J Nat Prod 2010; 73: 949-55.
[42]
Cidade HM, Nacimento MSJ, Pinto MM, Kijjoa A, Silva AM, Herz W. Artelastocarpin and carpelastofuran, two new flavones, and cytotoxicities of prenyl flavonoids from Artocarpus elasticus against three cancer cell lines. Planta Med 2001; 67: 867-70.
[43]
Seo E-K, Lee D, Shin YG, et al. Bioactive prenylated flavonoids from the stem bark of Artocarpus kemando. Arch Pharm Res 2003; 26: 124-7.
[44]
Musthapa I, Juliawaty LD, Syah YM, Hakim EH, Latip J, Ghisalberti EL. An oxepinoflavone from Artocarpus elasticus with cytotoxic activity against P-388 cells. Arch Pharm Res 2009; 32: 191.
[45]
Syah YM, Achmad SA, Ghisalberti EL, Hakim EH, Mujahidin D. Two new cytotoxic isoprenylated flavones, artoindonesianins U and V, from the heartwood of Artocarpus champeden. Fitoterapia 2004; 75: 134-40.
[46]
Wang Y-H, Hou A-J, Chen L, et al. New Isoprenylated Flavones, Artochamins A− E, and Cytotoxic Principles from Artocarpus chama. J Nat Prod 2004; 67: 757-61.
[47]
Lee C-c, Lin C-n, Jow G-m. Cytotoxic and apoptotic effects of prenylflavonoid artonin B in human acute lymphoblastic leukemia cells. Acta Pharmacol Sin 2006; 27: 1165.
[48]
Suhartati T, Achmad SA, Aimi N, et al. Artoindonesianin L, a new prenylated flavone with cytotoxic activity from Artocarpus rotunda. Fitoterapia 2001; 72: 912-8.
[49]
Dat NT, Binh PTX, Van Minh C, Huong HT, Lee JJ. Cytotoxic prenylated flavonoids from Morus alba. Fitoterapia 2010; 81: 1224-7.
[50]
Zhang M, Rong-Rong W, Man C, Zhang H-Q, Shi S, Zhang L-Y. A new flavanone glycoside with anti-proliferation activity from the root bark of Morus alba. Chin J Nat Med 2009; 7: 105-7.
[51]
Tan Y, Liu C, Chen R. Phenolic constituents from stem bark of Morus wittiorum and their anti-inflammation and cytotoxicity. Zhongguo Zhongyao Zazhi 2010; 35: 2700-3.
[52]
Zhen P, Ni G, Chen X, Chen R, Yang H, Yu D. Chemical constituents from Morus notabilis and their cytotoxic effect. Yao Xue Xue Bao 2015; 50: 579-82.
[53]
Zhang P-C, Wang S, Wu Y, Chen R-Y, Yu D-Q. Five New Diprenylated Flavonols from the Leaves of Broussonetia kazinoki. J Nat Prod 2001; 64: 1206-9.
[54]
Takashima J, Komiyama K, Ishiyama H. Kobayashi Ji, Ohsaki A. Brosimacutins J-M, four new flavonoids from Brosimum acutifolium and their cytotoxic activity. Planta Med 2005; 71: 654-8.
[55]
Tuan Anh HL, Tuan DT, Trang DT, et al. Prenylated isoflavones from Cudrania tricuspidata inhibit NO production in RAW 264.7 macrophages and suppress HL-60 cells proliferation. J Asian Nat Prod Res 2017; 19: 510-8.
[56]
Yuan H, Lu X, Ma Q, Li D, Xu G, Piao G. Flavonoids from Artemisia sacrorum Ledeb. and their cytotoxic activities against human cancer cell lines. Exp Ther Med 2016; 12: 1873-8.
[57]
Lone SH, Bhat KA, Naseer S, Rather RA, Khuroo MA, Tasduq SA. Isolation, cytotoxicity evaluation and HPLC-quantification of the chemical constituents from Artemisia amygdalina Decne. J Chromatogr B 2013; 940: 135-41.
[58]
Hajdú Z, Hohmann J, Forgo P, Máthé I, Molnár J, Zupkó I. Antiproliferative activity of Artemisia asiatica extract and its constituents on human tumor cell lines. Planta Med 2014; 80: 1692-7.
[59]
Ahmed SA, Kamel EM. Cytotoxic activities of flavonoids from Centaurea scoparia. Sci World J 2014; 2014: 274207.
[60]
Alarif WM, Abdel-Lateff A, Al-Abd AM, et al. Selective cytotoxic effects on human breast carcinoma of new methoxylated flavonoids from Euryops arabicus grown in Saudi Arabia. Eur J Med Chem 2013; 66: 204-10.
[61]
Hajdú Z, Zupkó I, Réthy B, Forgo P, Hohmann J. Bioactivity-guided isolation of cytotoxic sesquiterpenes and flavonoids from Anthemis ruthenica. Planta Med 2010; 76: 94-6.
[62]
Kuroda M, Yokosuka A, Kobayashi R, et al. Sesquiterpenoids and flavonoids from the aerial parts of Tithonia diversifolia and their cytotoxic activity. Chem Pharm Bull 2007; 55: 1240-4.
[63]
Cabrera J, Saavedra E, del Rosario H, et al. Gardenin B-induced cell death in human leukemia cells involves multiple caspases but is independent of the generation of reactive oxygen species. Chem Biol Interact 2016; 256: 220-7.
[64]
Trifunović S, Vajs V, Juranić Z, et al. Cytotoxic constituents of Achillea clavennae from Montenegro. Phytochemistry 2006; 67: 887-93.
[65]
Salama MM, Kandil ZA, Islam WT. Cytotoxic compounds from the leaves of Gaillardia aristata Pursh. growing in Egypt. Nat Prod Res 2012; 26: 2057-62.
[66]
Sinha S, Amin H, Nayak D, et al. Assessment of microtubule depolymerization property of flavonoids isolated from Tanacetum gracile in breast cancer cells by biochemical and molecular docking approach. Chem Biol Interact 2015; 239: 1-11.
[67]
Wang Z-x, Cheng M-c, Zhang X-z, et al. Cytotoxic biflavones from Stellera chamaejasme. Fitoterapia 2014; 99: 334-40.
[68]
Li J, Zhang J-J, Pang X-X. ZhengChen X-L, Gan L-S. Biflavanones with anti-proliferative activity against eight human solid tumor cell lines from Stellera chamaejasme. Fitoterapia 2014; 93: 163-7.
[69]
Tian Q, Li J, Xie X, et al. Stereospecific induction of nuclear factor-κB activation by isochamaejasmin. Mol Pharmacol 2005; 68: 1534-42.
[70]
Sun Q, Wang D, Li F-F, et al. Cytotoxic prenylated flavones from the stem and root bark of Daphne giraldii. Bioorg Med Chem Lett 2016; 26: 3968-72.
[71]
Wang D, Sun Q, Wu J, et al. A new Prenylated Flavonoid i nduces G0/G1 arrest and apoptosis through p38/JNK MAPK pathways in Human Hepatocellular Carcinoma cells. Sci Rep 2017; 7: 5736.
[72]
Tanjung M, Hakim EH, Mujahidin D, Hanafi M, Syah YM. Macagigantin, a farnesylated flavonol from Macaranga gigantea. J Asian Nat Prod Res 2009; 11: 929-32.
[73]
Yang D-S, Peng W-B, Yang Y-P, Liu K-C, Li X-L, Xiao W-L. Cytotoxic prenylated flavonoids from Macaranga indica. Fitoterapia 2015; 103: 187-91.
[74]
Tanjung M, Hakim EH, Latip J, Syah YM. Dihydroflavonol and flavonol derivatives from Macaranga recurvata. Nat Prod Commun 2012; 7: 1309-10.
[75]
Chaabi M, Freund-Michel V, Frossard N, Randriantsoa A, Andriantsitohaina R, Lobstein A. Anti-proliferative effect of Euphorbia stenoclada in human airway smooth muscle cells in culture. J Ethnopharmacol 2007; 109: 134-9.
[76]
El-Desouky S, Ryu SY, Kim Y-K. A new cytotoxic acylated apigenin glucoside from Phyllanthus emblica L. Nat Prod Res 2008; 22: 91-5.
[77]
Ahmed H, Moawad A, Owis A, AbouZid S, Ahmed O. Flavonoids of Calligonum polygonoides and their cytotoxicity. Pharm Biol 2016; 54: 2119-26.
[78]
Smolarz H, Budzianowski J, Bogucka‐Kocka A, Kocki J, Mendyk E. Flavonoid glucuronides with anti‐leukaemic activity from Polygonum amphibium L. Phytochem Anal 2008; 19: 506-13.
[79]
Hussein AA, Barberena I, Correa M, Coley PD, Solis PN, Gupta MP. Cytotoxic Flavonol Glycosides from Triplaris cumingiana. J Nat Prod 2005; 68: 231-3.
[80]
Sonoda M, Nishiyama T, Matsukawa Y, Moriyasu M. Cytotoxic activities of flavonoids from two Scutellaria plants in Chinese medicine. J Ethnopharmacol 2004; 91: 65-8.
[81]
Awale S, Linn TZ, Li F, et al. Identification of chrysoplenetin from Vitex negundo as a potential cytotoxic agent against PANC‐1 and a panel of 39 human cancer cell lines (JFCR‐39). Phytother Res 2011; 25: 1770-5.
[82]
Tundis R, Loizzo MR, Menichini F, Bonesi M, Colica C, Menichini F. In vitro cytotoxic activity of extracts and isolated constituents of salvia leriifolia Benth. against a panel of human cancer cell lines. Chem Biodivers 2011; 8: 1152-62.
[83]
Huong D, Luong D, Thao T, Sung T. A new flavone and cytotoxic activity of flavonoid constituents isolated from Miliusa balansae (Annonaceae). Int J Pharma Sci 2005; 60: 627-9.
[84]
Bajgai SP, Prachyawarakorn V, Mahidol C, Ruchirawat S, Kittakoop P. Hybrid flavan-chalcones, aromatase and lipoxygenase inhibitors, from Desmos cochinchinensis. Phytochemistry 2011; 72: 2062-7.
[85]
Kuete V, Sandjo LP, Mbaveng AT, Zeino M, Efferth T. Cytotoxicity of compounds from Xylopia aethiopica towards multi-factorial drug-resistant cancer cells. Phytomedicine 2015; 22: 1247-54.
[86]
Hafez Ghoran S, Saeidnia S, Babaei E, Kiuchi F, Hussain H. Scillapersicene: A new homoisoflavonoid with cytotoxic activity from the bulbs of Scilla persica HAUSSKN. Nat Prod Res 2016; 30: 1309-14.
[87]
Alali F, El-Elimat T, Albataineh H, et al. Cytotoxic homoisoflavones from the bulbs of Bellevalia eigii. J Nat Prod 2015; 78: 1708-15.
[88]
Liu J, Mei W-L, Wu J, Zhao Y-X, Peng M, Dai H-F. A new cytotoxic homoisoflavonoid from Dracaena cambodiana. J Asian Nat Prod Res 2009; 11: 192-5.
[89]
Wu J, Du J, Fu X, et al. Icaritin, a novel FASN inhibitor, exerts anti-melanoma activities through IGF-1R/STAT3 signaling. Oncotarget 2016; 7: 51251.
[90]
Sun L, Peng Q, Qu L, Gong L, Si J. Anticancer agent icaritin induces apoptosis through caspase-dependent pathways in human hepatocellular carcinoma cells. Mol Med Rep 2015; 11: 3094-100.
[91]
Ren F-C, Jiang X-J, Wen S-Z, Wang L-X, Li X-M, Wang F. Prenylated 2-Phenoxychromones and Flavonoids from Epimedium brevicornum and Revised Structures of Epimedonins A and B. J Nat Prod 2018; 81(1): 16-21.
[92]
Tomczyk M, Drozdowska D, Bielawska A, Bielawski K, Gudej J. Human DNA topoisomerase inhibitors from Potentilla argentea and their cytotoxic effect against MCF-7. Int J Pharma Sci 2008; 63: 389-93.
[93]
Hu Q-F, Zhou B, Huang J-M, et al. Cytotoxic oxepinochromenone and flavonoids from the flower buds of Rosa rugosa. J Nat Prod 2013; 76: 1866-71.
[94]
Ahmad S, Sukari MA, Ismail N, et al. Phytochemicals from Mangifera pajang Kosterm and their biological activities. BMC Complement Altern Med 2015; 15: 83.
[95]
Konan NA, Lincopan N, Díaz IEC, et al. Cytotoxicity of cashew flavonoids towards malignant cell lines. Exp Toxicol Pathol 2012; 64: 435-40.
[96]
Shyh-Yuan L. A novel cytotoxic C-methylated biflavone from the stem of Cephalotaxus wilsoniana. Notes 2000; 48: 440-1.
[97]
Kuo Y-H, Hwang S-Y, Kuo L-MY, Lee Y-L, Li S-Y, Shen Y-C. A novel cytotoxic C-methylated biflavone, taiwanhomoflavone-B from the twigs of Cephalotaxus wilsoniana. Chem Pharm Bull 2002; 50: 1607-8.
[98]
Chen J-J, Duh C-Y, Chen J-F. New cytotoxic biflavonoids from Selaginella delicatula. Planta Med 2005; 71: 659-65.
[99]
Cao Y, Tan N-H, Chen J-J. Z et al. Bioactive flavones and biflavones from Selaginella moellendorffii Hieron. Fitoterapia 2010; 81: 253-8.
[100]
Kitdamrongtham W, Ishii K, Ebina K, et al. Limonoids and Flavonoids from the Flowers of Azadirachta indica var. siamensis, and Their Melanogenesis‐Inhibitory and Cytotoxic Activities. Chem Biodivers 2014; 11: 73-84.
[101]
Roy S, Banerjee B, Vedasiromoni J. Cytotoxic and apoptogenic effect of Swietenia mahagoni (L.) Jacq. leaf extract in human leukemic cell lines U937, K562 and HL-60. Environ Toxicol Pharmacol 2014; 37: 234-47.
[102]
Noreen H, Farman M, McCullagh JS. Bioassay-guided isolation of cytotoxic flavonoids from aerial parts of Coronopus didymus. J Ethnopharmacol 2016; 194: 971-80.
[103]
Lee YJ, Kim NS, Kim H, et al. Cytotoxic and anti-inflammatory constituents from the seeds of Descurainia sophia. Arch Pharm Res 2013; 36: 536-41.
[104]
Lin A-S, Chang F-R, Wu C-C, Liaw C-C, Wu Y-C. New cytotoxic flavonoids from Thelypteris torresiana. Planta Med 2005; 71: 867-70.
[105]
Zhao Z, Ruan J, Jin J, et al. Flavan-4-ol Glycosides from the Rhizomes of Abacopteris p enangiana. J Nat Prod 2006; 69: 265-8.
[106]
Kim J-A, Lau EK, Pan L, de Blanco EJC. NF-κB inhibitors from Brucea javanica exhibiting intracellular effects on reactive oxygen species. Anticancer Res 2010; 30: 3295-300.
[107]
Al-Ashaal HA, El-Sheltawy ST. Antioxidant capacity of hesperidin from citrus peel using electron spin resonance and cytotoxic activity against human carcinoma cell lines. Pharm Biol 2011; 49: 276-82.
[108]
Yue R, Li B, Shen Y, et al. 6-C-methyl flavonoids isolated from Pinus densata inhibit the proliferation and promote the apoptosis of the HL-60 human promyelocytic leukaemia cell line. Planta Med 2013; 79: 1024-30.
[109]
Tang B-Q, Huang S-S, Liang Y-E, et al. Two new flavans from the roots of Dianella ensifolia (L.) DC. Nat Prod Res 2017; 31: 1561-5.
[110]
Bai N, He K, Roller M, et al. Flavonoid glycosides from Microtea debilis and their cytotoxic and anti-inflammatory effects. Fitoterapia 2011; 82: 168-72.
[111]
Zhang L, Gao H-y, Baba M, et al. Extracts and compounds with anti-diabetic complications and anti-cancer activity from Castanea mollissina Blume (Chinese chestnut). BMC Complement Altern Med 2014; 14: 422.
[112]
Rajkapoor B, Murugesh N, Rama Krishna D. Cytotoxic activity of a flavanone from the stem of Bauhinia variegata Linn. Nat Prod Res 2009; 23: 1384-9.
[113]
Nawwar M, Swilam N, Hashim A, Al-Abd A, Abdel-Naim A, Lindequist U. Cytotoxic isoferulic acidamide from Myricaria germanica (Tamaricaceae). Plant Signal Behav 2013; 8: e22642.
[114]
Abdullah FO, Hussain FH, Clericuzio M, Porta A, Vidari G. A New Iridoid Dimer and Other Constituents from the Traditional Kurdish Plant Pterocephalus nestorianus Nábělek. Chem Biodivers 2017; 14.
[115]
Hahm E-R, Park S, Yang C-H. 7, 8-dihydroxyflavanone as an inhibitor for Jun-Fos-DNA complex formation and its cytotoxic effect on cultured human cancer cells. Nat Prod Res 2003; 17: 431-6.
[116]
Lin H-Y, Hou S-C, Chen S-C, et al. (−)-Epigallocatechin gallate induces Fas/CD95-mediated apoptosis through inhibiting constitutive and IL-6-induced JAK/STAT3 signaling in head and neck squamous cell carcinoma cells. J Agric Food Chem 2012; 60: 2480-9.
[117]
Kuo Y-J, Hwang S-Y, Wu M-D, et al. Cytotoxic constituents from Podocarpus fasciculus. Chem Pharm Bull 2008; 56: 585-8.
[118]
Hamdy A-HA, Mettwally WS, El Fotouh MA, et al. Bioactive phenolic compounds from the Egyptian Red Sea seagrass Thalassodendron ciliatum. Z Naturforsch C 2012; 67: 291-6.
[119]
Chou T-H, Chen J-J, Lee S-J, Chiang MY, Yang C-W, Chen I-S. Cytotoxic flavonoids from the leaves of Cryptocarya chinensis. J Nat Prod 2010; 73: 1470-5.
[120]
Sufian AS, Ramasamy K, Ahmat N, Zakaria ZA, Yusof MIM. Isolation and identification of antibacterial and cytotoxic compounds from the leaves of Muntingia calabura L. J Ethnopharmacol 2013; 146: 198-204.
[121]
Shen C-C, Cheng J-J, Lay H-L, et al. Cytotoxic apigenin derivatives from Chrysopogon aciculatis. J Nat Prod 2012; 75: 198-201.
[122]
Rosselli S, Bruno M, Maggio A, et al. Cytotoxic geranylflavonoids from Bonannia graeca. Phytochemistry 2011; 72: 942-5.
[123]
Do LT, Aree T, Siripong P, Pham TN, Nguyen PK, Tip-pyang S. Bougainvinones A–H, peltogynoids from the stem bark of purple Bougainvillea spectabilis and their cytotoxic activity. J Nat Prod 2016; 79: 939-45.
[124]
Ndongo JT, Issa ME, Messi AN, et al. Cytotoxic flavonoids and other constituents from the stem bark of Ochna schweinfurthiana. Nat Prod Res 2015; 29: 1684-7.
[125]
Dar AA, Dangroo NA, Raina A, et al. Biologically active xanthones from Codonopsis ovata. Phytochemistry 2016; 132: 102-8.
[126]
Freitas GC, Batista Jr J.M., Franchi Jr G.C., et al. Cytotoxic non-aromatic B-ring flavanones from Piper carniconnectivum C. DC. Phytochemistry 2014; 97: 81-7.
[127]
Tundis R, Deguin B, Loizzo MR, et al. Potential antitumor agents: Flavones and their derivatives from Linaria reflexa Desf. Bioorg Med Chem Lett 2005; 15: 4757-60.
[128]
Dang NH, Chung ND, Tuan HM, Hiep NT, Dat NT. Cytotoxic Homoisoflavonoids from Ophiopogon japonicus Tubers. Chem Pharm Bull 2017; 65: 204-7.
[129]
Xie G-Y, Qin X-Y, Liu R, et al. New isoflavones with cytotoxic activity from the rhizomes of Iris germanica L. Nat Prod Res 2013; 27: 2173-7.
[130]
Cao S, Norris A, Miller JS, et al. Cytotoxic compounds of Physena madagascariensis from the Madagascar rain forest. Nat Prod Res 2006; 20: 1157-63.
[131]
Abdel-salam NA, Ghazy NM, Sallam SM, et al. Flavonoids of Alcea rosea L. and their immune stimulant, antioxidant and cytotoxic activities on hepatocellular carcinoma HepG-2 cell line. Nat Prod Res 2018; 32: 702-6.
[132]
Ismail N, Alam M. A novel cytotoxic flavonoid glycoside from Physalis angulata. Fitoterapia 2001; 72: 676-9.
[133]
Seito LN, Ruiz ALTG, Vendramini‐Costa D, et al. Antiproliferative activity of three methoxylated flavonoids isolated from Zeyheria montana Mart.(Bignoniaceae) leaves. Phytother Res 2011; 25: 1447-50.
[134]
Heim KE, Tagliaferro AR, Bobilya DJ. Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships. J Nutr Biochem 2002; 13: 572-84.
[135]
Kumar NB, Pow-Sang J, Egan KM, et al. Randomized, placebo-controlled trial of green tea catechins for prostate cancer prevention Cancer Prev Res 2015: canprevres. 0324 2014.
[136]
Zhao H, Zhu W, Xie P, et al. A phase I study of concurrent chemotherapy and thoracic radiotherapy with oral epigallocatechin-3-gallate protection in patients with locally advanced stage III non-small-cell lung cancer. Radiother Oncol 2014; 110: 132-6.
[137]
Hoensch H, Groh B, Edler L, Kirch W. Prospective cohort comparison of flavonoid treatment in patients with resected colorectal cancer to prevent recurrence. World J Gastroenterol 2008; 14: 2187.
[138]
Zhao H, Zhu W, Jia L, et al. Phase I study of topical epigallocatechin-3-gallate (EGCG) in patients with breast cancer receiving adjuvant radiotherapy. Br J Radiol 2015; 89: 20150665.
[139]
Elyasi S, Hosseini S, Niazi Moghadam MR, Aledavood SA, Karimi G. Effect of oral silymarin administration on prevention of radiotherapy induced mucositis: a randomized, double‐blinded, placebo‐controlled clinical trial. Phytother Res 2016; 30: 1879-85.
[140]
Flaig TW, Glodé M, Gustafson D, et al. A study of high‐dose oral silybin‐phytosome followed by prostatectomy in patients with localized prostate cancer. Prostate 2010; 70: 848-55.
[141]
Lazzeroni M, Guerrieri-Gonzaga A, Gandini S, et al. A presurgical study of oral silybin-phosphatidylcholine in patients with early breast cancer. Cancer Prev Res 2016; 9: 89-95.
[142]
Lazarevic B, Hammarström C, Yang J, et al. The effects of short-term genistein intervention on prostate biomarker expression in patients with localised prostate cancer before radical prostatectomy. Br J Nutr 2012; 108: 2138-47.
[143]
Messing E, Gee JR, Saltzstein DR, et al. Young JM. A phase 2 cancer chemoprevention biomarker trial of isoflavone G-2535 (genistein) in presurgical bladder cancer patients. Cancer Prev Res 2013; 11: 107-12.
[144]
Miltyk W, Craciunescu CN, Fischer L, et al. Lack of significant genotoxicity of purified soy isoflavones (genistein, daidzein, and glycitein) in 20 patients with prostate cancer. Am J Clin Nutr 2003; 77: 875-82.
[145]
Howes JB, de Souza PL, West L, Huang LJ, Howes LG. Pharmacokinetics of phenoxodiol, a novel isoflavone, following intravenous administration to patients with advanced cancer. BMC Clin Pharmacol 2011; 11: 1.
[146]
de Souza PL, Liauw W, Links M, Pirabhahar S, Kelly G, Howes LG. Phase I and pharmacokinetic study of weekly NV06 (Phenoxodiol™), a novel isoflav-3-ene, in patients with advanced cancer. Cancer Chemother Pharmacol 2006; 58: 427-33.
[147]
Choueiri T, Mekhail T, Hutson T, Ganapathi R, Kelly G, Bukowski R. Phase I trial of phenoxodiol delivered by continuous intravenous infusion in patients with solid cancer. Ann Oncol 2006; 17: 860-5.
[148]
Kelly MG, Mor G, Husband A, et al. Phase II evaluation of phenoxodiol in combination with cisplatin or paclitaxel in women with platinum/taxane-refractory/resistant epithelial ovarian, fallopian tube, or primary peritoneal cancers. Int J Gynecol Cancer 2011; 21: 633-9.
[149]
Cruz–Correa M, Shoskes DA, Sanchez P, et al. Combination treatment with curcumin and quercetin of adenomas in familial adenomatous polyposis. Clin Gastroenterol Hepatol 2006; 4: 1035-8.
[150]
Hofmeister CC, Poi M, Bowers MA, et al. A phase I trial of flavopiridol in relapsed multiple myeloma. Cancer Chemother Pharmacol 2014; 73: 249-57.
[151]
Liu G, Gandara DR, Lara PN, et al. A Phase II trial of flavopiridol (NSC# 649890) in patients with previously untreated metastatic androgen-independent prostate cancer. Clin Cancer Res 2004; 10: 924-8.
[152]
Stadler WM, Vogelzang NJ, Amato R, et al. Flavopiridol, a novel cyclin-dependent kinase inhibitor, in metastatic renal cancer: a University of Chicago Phase II Consortium study. J Clin Oncol 2000; 18: 371-5.
[153]
George S, Kasimis BS, Cogswell J, et al. Phase I Study of Flavopiridol in Combination with Paclitaxel and Carboplatin in Patients with Non–Small-Cell Lung Cancer. Clin Lung Cancer 2008; 9: 160-5.
[154]
Shapiro GI, Supko JG, Patterson A, et al. A phase II trial of the cyclin-dependent kinase inhibitor flavopiridol in patients with previously untreated stage IV non-small cell lung cancer. Clin Cancer Res 2001; 7: 1590-9.
[155]
Kouroukis CT, Belch A, Crump M, et al. Flavopiridol in untreated or relapsed mantle-cell lymphoma: results of a phase II study of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 2003; 21: 1740-5.
[156]
Ramaswamy B, Phelps MA, Baiocchi R, et al. A dose-finding, pharmacokinetic and pharmacodynamic study of a novel schedule of flavopiridol in patients with advanced solid tumors. Invest New Drugs 2012; 30: 629-38.
[157]
Byrd JC, Peterson BL, Gabrilove J, et al. Treatment of relapsed chronic lymphocytic leukemia by 72-hour continuous infusion or 1-hour bolus infusion of flavopiridol: results from Cancer and Leukemia Group B study 19805. Clin Cancer Res 2005; 11: 4176-81.
[158]
Schwartz GK, Ilson D, Saltz L, et al. Phase II study of the cyclin-dependent kinase inhibitor flavopiridol administered to patients with advanced gastric carcinoma. J Clin Oncol 2001; 19: 1985-92.
[159]
Senderowicz AM, Headlee D, Stinson SF, et al. Phase I trial of continuous infusion flavopiridol, a novel cyclin-dependent kinase inhibitor, in patients with refractory neoplasms. J Clin Oncol 1998; 16: 2986-99.
[160]
Flinn IW, Byrd JC, Bartlett N, et al. Flavopiridol administered as a 24-hour continuous infusion in chronic lymphocytic leukemia lacks clinical activity. Leuk Res 2005; 29: 1253-7.
[161]
Burdette-Radoux S, Tozer RG, Lohmann RC, et al. Phase II trial of flavopiridol, a cyclin dependent kinase inhibitor, in untreated metastatic malignant melanoma. Invest New Drugs 2004; 22: 315-22.
[162]
Miyanaga N, Akaza H, Hinotsu S, et al. Prostate cancer chemoprevention study: an investigative randomized control study using purified isoflavones in men with rising prostate‐specific antigen. Cancer Res 2012; 103: 125-30.
[163]
Pagano L, Teofili L, Mele L, et al. Oral ipriflavone (7-isopropoxyisoflavone) treatment for elderly patients with resistant acute leukemias. Ann Oncol 1999; 10: 124-5.
[164]
David AVA, Arulmoli R, Parasuraman S. Overviews of biological importance of quercetin: A bioactive flavonoid. Pharmacogn Rev 2016; 10: 84.
[165]
Meena MC, Patni V. Isolation and identification of flavonoid” quercetin” from Citrullus colocynthis (Linn.) Schrad. Asian J Exp Sci 2008; 22: 137-42.
[166]
Handoussa H, Hanafi R, Eddiasty I, et al. Anti-inflammatory and cytotoxic activities of dietary phenolics isolated from Corchorus olitorius and Vitis vinifera. J Funct Foods 2013; 5: 1204-16.
[167]
Xiao J. Dietary flavonoid aglycones and their glycosides: Which show better biological significance? Crit Rev Food Sci Nutr 2017; 57: 1874-905.
[168]
Leonarduzzi G, Testa G, Sottero B, Gamba P, Poli G. Design and development of nanovehicle-based delivery systems for preventive or therapeutic supplementation with flavonoids. Curr Med Chem 2010; 17: 74-95.
[169]
Manacha C, Donovan JL. Pharmacokinetics and Metabolism of Dietary Flavonoids in Humans. Free Radic Res 2004; 38: 771-85.
[170]
Erlund I. Review of the flavonoids quercetin, hesperetin, and naringenin. Dietary sources, bioactivities, bioavailability, and epidemiology. Nutr Res 2004; 24: 851-74.
[171]
Chen Z, Zheng S, Li L, Jiang H. Metabolism of flavonoids in human: a comprehensive review. Curr Drug Metab 2014; 15: 48-61.
[172]
Yanez JA, Remsberg CM, Miranda ND, Vega‐Villa KR, Andrews PK, Davies NM. Pharmacokinetics of selected chiral flavonoids: hesperetin, naringenin and eriodictyol in rats and their content in fruit juices. Biopharm Drug Dispos 2001; 41: 492-9.
[173]
Hollman PCH, Katan MB. Absorption, metabolism and health effects of dietary flavonoids in man. Biomed Pharmacother 1997; 51: 305-10.
[174]
Walle T. Absorption and metabolism of flavonoids. Free Radic Biol Med 2004; 36: 829-37.
[175]
Yanez JA, Sayre CL, Martinez SE, Davies NM. Chiral Methods of Flavonoid Analysis. Flavonoid Pharmacokinetics: Methods of Analysis, Preclinical and Clinical Pharmacokinetics, Safety, and Toxicology. Bioorg Med Chem 2012; 117-59.
[176]
Taleghani A, Nasseri MA, Iranshahi M. Synthesis of dual-action parthenolide prodrugs as potent anticancer agents. Bioorg Chem 2017; 71: 128-34.
[177]
Plochmann K, Korte G, Koutsilieri E, et al. Structure–activity relationships of flavonoid-induced cytotoxicity on human leukemia cells. Arch Biochem Biophys 2007; 460: 1-9.
[178]
Lopez-Lazaro M. Flavonoids as anticancer agents: structure-activity relationship study. Curr Med Chem Anticancer Agents 2002; 6: 691-714.
[179]
Lopez-Lazaro M, Galvez M, Martín-Cordero C, Ayuso MJ. Cytotoxicity of flavonoids on cancer cell lines: Structure-activity relationship. Stud Nat Prod Chem 2002; 27: 891-932.
[180]
Cardenas M, Marder M, Blank VC, Roguin LP. Antitumor activity of some natural flavonoids and synthetic derivatives on various human and murine cancer cell lines. Bioorg Med Chem 2006; 14: 2966-71.
[181]
Menezes JC, Orlikova B, Morceau F, Diederich M. Natural and synthetic flavonoids: structure–activity relationship and chemotherapeutic potential for the treatment of leukemia. Crit Rev Food Sci Nutr 2016; 56: S4-S28.
[182]
Li F, Awale S, Tezuka Y, Kadota S. Cytotoxic constituents from Brazilian red propolis and their structure–activity relationship. Bioorg Med Chem 2008; 16: 5434-40.
[183]
Zhong JQ, Li B, Jia Q, Li YM, Zhu WL, Chen KX. Advances in the structure-activity relationship study of natural flavonoids and its derivatives. Yao Xue Xue Bao 2011; 46: 622-30.
[184]
Rice-Evans CA, Miller NJ, Paganga G. Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radic Biol Med 1996; 20: 933-56.
[185]
Amic D, Davidovic-Amic D, Beslo D, Trinajstic N. Structure-Radical Scavenging Activity Relationships of Flavonoids. Croat Chem Acta 2003; 76: 55-61.
[186]
Chen JW, Zhu ZQ, Hu TX, Zhu DY. Structure-activity relationship of natural flavonoids in hydroxyl radical-scavenging. Acta Pharmacol Sin 2002; 23: 667-72.

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