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Review Articles

Structural diversity, biosynthesis, and health-promoting properties of brown algal meroditerpenoids

ORCID Icon, , & ORCID Icon
Pages 1238-1259 | Received 29 Mar 2021, Accepted 08 Sep 2021, Published online: 07 Dec 2021

References

  • Blunt JW, Copp BR, Keyzers RA, et al. Marine natural products. Nat Prod Rep. 2016;33(3):382–431.
  • Fernando IPS, Nah J-W, Jeon Y-J. Potential anti-inflammatory natural products from marine algae. Environ Toxicol Pharmacol. 2016;48:22–30.
  • Reddy P, Urban S. Meroditerpenoids from the Southern Australian marine brown alga Sargassum fallax. Phytochemistry. 2009;70(2):250–255.
  • Fenical W, Norris JN. Chemotaxonomy in marine algae: chemical separation of some Laurencia species (Rhodophyta) from the Gulf of California. J Phycol. 1975;11(1):104–108.
  • Amico V. Marine brown algae of family cystoseiraceae: chemistry and chemotaxonomy. Phytochemistry. 1995;39(6):1257–1279.
  • Evans HM, Bishop KS. On the existence of a hitherto unrecognized dietary factor essential for reproduction. Science. 1922;56(1458):650–651.
  • Peng Y, Hu J, Yang B, et al. Chapter 5 – chemical composition of seaweeds. In: Troy DJ, editor. Seaweed sustainability. San Diego (CA): Academic Press; 2015. p. 79–124.
  • Jang KH, Lee BH, Choi BW, et al. Chromenes from the brown alga Sargassum siliquastrum. J Nat Prod. 2005;68(5):716–723.
  • Matsuda Y, Abe I. Biosynthesis of fungal meroterpenoids. Nat Prod Rep. 2016;33(1):26–53.
  • Cornforth J. Terpenoid biosynthesis. Chem Br. 1968;4(3):102–106.
  • Kato T, Kumanireng AS, Ichinose I, et al. Structure and synthesis of active component from a marine alga, Sargassum tortile, which induces the settling of swimming larvae of Coryne uchidai. Chem Lett. 1975;4(4):335–338.
  • Birringer M, Siems K, Maxones A, et al. Natural 6-hydroxy-chromanols and-chromenols: structural diversity, biosynthetic pathways and health implications. RSC Adv. 2018;8(9):4803–4841.
  • Gálvez-Valdivieso G, Pineda M, Aguilar M. Functional characterization and expression analysis of P-hydroxyphenylpyruvate dioxygenase from the green alga Chlamydomonas reinhardtii (Chlorophyta). J Phycol. 2010;46(2):297–308.
  • Lushchak VI, Semchuk NM. Tocopherol biosynthesis: chemistry, regulation and effects of environmental factors. Acta Physiol Plant. 2012;34(5):1607–1628.
  • Sattler SE, Cahoon EB, Coughlan SJ, et al. Characterization of tocopherol cyclases from higher plants and cyanobacteria. Evolutionary implications for tocopherol synthesis and function. Plant Physiol. 2003;132(4):2184–2195.
  • Kruk J, Holländer-Czytko H, Oettmeier W, et al. Tocopherol as singlet oxygen scavenger in photosystem II. J Plant Physiol. 2005;162(7):749–757.
  • Brigelius-Flohe R, Traber MG. Vitamin E: function and metabolism. FASEB J. 1999;13(10):1145–1155.
  • Sabry OMM, Andrews S, McPhail KL, et al. Neurotoxic meroditerpenoids from the tropical marine brown alga Stypopodium flabelliforme. J Nat Prod. 2005;68(7):1022–1030.
  • Gerwick WH, Fenical W, Norris JN. Chemical variation in the tropical seaweed Stypopodium zonale (Dictyotaceae). Phytochemistry. 1985;24(6):1279–1283.
  • Dorta E, Dı́az-Marrero AR, Cueto M, et al. On the relative stereochemistry of atomaric acid and related compounds. Tetrahedron. 2003;59(12):2059–2062.
  • Francisco C, Banaigs B, Teste J, et al. Mediterraneols: a novel biologically active class of rearranged diterpenoid metabolites from Cystoseira mediterranea (Pheophyta). J Org Chem. 1986;51(7):1115–1120.
  • Fadli M, Aracil J-M, Jeanty G, et al. Méditerranéol E: proposition de structure pour un méroditerpène transposé de l'algue brune Cystoseira mediaterranea. Tetrahedron Lett. 1991;32(22):2477–2480.
  • Valls R, Piovetti L, Praud A. The use of diterpenoids as chemotaxonomic markers in the genus cystoseira. Hydrobiologia. 1993;260–261(1):549–556.
  • Brkljača R, Urban S. Chemical profiling (HPLC-NMR & HPLC-MS), isolation, and identification of bioactive meroditerpenoids from the Southern Australian marine brown alga sargassum paradoxum. Mar Drugs. 2014;13(1):102–127.
  • Gouveia VLM, Seca AML, Barreto MC, et al. Cytotoxic meroterpenoids from the macroalga Cystoseira abies-marina. Phytochem Lett. 2013;6(4):593–597.
  • de los Reyes C, Ortega MJ, Zbakh H, et al. Cystoseira usneoides: a brown alga rich in antioxidant and anti-inflammatory meroditerpenoids. J Nat Prod. 2016;79(2):395–405.
  • Numata A, Kanbara S, Takahashi C, et al. A cytotoxic principle of the brown alga sargassum tortile and structures of chromenes. Phytochemistry. 1992;31(4):1209–1213.
  • Hill RA. Marine natural products. Annu Rep Prog Chem B. 2009;105:150–166.
  • Areche C, San-Martín A, Rovirosa J, et al. An unusual halogenated meroditerpenoid from Stypopodium flabelliforme: studies by NMR spectroscopic and computational methods. Phytochemistry. 2009;70(10):1315–1320.
  • Horie S, Tsutsumi S, Takada Y, et al. Antibacterial quinone metabolites from the brown alga, Sargassum sagamianum. BCSJ. 2008;81(9):1125–1130.
  • Iwashima M, Mori J, Ting X, et al. Antioxidant and antiviral activities of plastoquinones from the brown alga Sargassum micracanthum, and a new chromene derivative converted from the plastoquinones. Biol Pharm Bull. 2005;28(2):374–377.
  • Kim MC, Kwon HC, Kim SN, et al. Plastoquinones from Sargassum yezoense; chemical structures and effects on the activation of peroxisome proliferator-activated receptor gamma. Chem Pharm Bull. 2011;59(7):834–838.
  • Niwa H, Kurimoto S-I, Kubota T, et al. Macrocarquinoids A–C, new meroterpenoids from sargassum macrocarpum. J Nat Med. 2021;75(1):194–200.
  • Im Lee J, Seo Y. Chromanols from Sargassum siliquastrum and their antioxidant activity in HT 1080 cells. Chem Pharm Bull. 2011;59(6):757–761.
  • Iwashima MM, Tako N, Hayakawa T, et al. New chromane derivatives isolated from the brown alga, Sargassum micracanthum. Chem Pharm Bull. 2008;56(1):124–128.
  • Seo Y, Park KE, Kim YA, et al. Isolation of tetraprenyltoluquinols from the brown alga Sargassum thunbergii. Chem Pharm Bull. 2006;54(12):1730–1733.
  • Bartosińska E, Buszewska-Forajta M, Siluk D. GC-MS and LC-MS approaches for determination of tocopherols and tocotrienols in biological and food matrices. J Pharm Biomed Anal. 2016;127:156–169.
  • Safafar H, Van Wagenen J, Møller P, et al. Carotenoids, phenolic compounds and tocopherols contribute to the antioxidative properties of some microalgae species grown on industrial wastewater. Mar Drugs. 2015;13(12):7339–7356.
  • Yang P, Liu D-Q, Liang T-J, et al. Bioactive constituents from the green alga Caulerpa racemosa. Bioorg Med Chem. 2015;23(1):38–45.
  • Penicooke N, Walford K, Badal S, et al. Antiproliferative activity and absolute configuration of zonaquinone acetate from the Jamaican alga Stypopodium zonale. Phytochemistry. 2013;87:96–101.
  • Choi H, Hwang H, Chin J, et al. Tuberatolides, potent FXR antagonists from the Korean marine tunicate Botryllus tuberatus. J Nat Prod. 2011;74(1):90–94.
  • Seo Y-W, Park K-E, Nam T-J. Isolation of a new chromene from the brown alga Sargassum thunbergii. Bull Korean Chem Soc. 2007;28(10):1831–1833.
  • Silva DH, Zhang Y, Santos LA, et al. Lipoperoxidation and cyclooxygenases 1 and 2 inhibitory compounds from Iryanthera juruensis. J Agric Food Chem. 2007;55(7):2569–2574.
  • Tsuchiya N, Sato A, Haruyama H, et al. Nahocols and isonahocols, endothelin antagonists from the brown alga, Sargassum autumnale. Phytochemistry. 1998;48(6):1003–1011.
  • Jung M, Jang KH, Kim B, et al. Meroditerpenoids from the brown alga Sargassum siliquastrum. J Nat Prod. 2008;71(10):1714–1719.
  • González AG, Darias J, Martín JD. Taondiol, a new component from Taonia atomaria. Tetrahedron Lett. 1971;12(29):2729–2732.
  • Areche C, Benites J, Cornejo A, et al. Seco-Taondiol, an unusual meroterpenoid from the Chilean seaweed Stypopodium flabelliforme and its gastroprotective effect in mouse model. Mar Drugs. 2015;13(4):1726–1738.
  • Areche C, San-Martín A, Rovirosa J, et al. Stereostructure reassignment and absolute configuration of isoepitaondiol, a meroditerpenoid from Stypopodium flabelliforme. J Nat Prod. 2010;73(1):79–82.
  • Soares AR, Duarte HM, Tinnoco LW, et al. Intraspecific variation of meroditerpenoids in the brown alga Stypopodium zonale guiding the isolation of new compounds. Rev Brasil Farmacogn. 2015;25(6):627–633.
  • Mendes G, Soares AR, Sigiliano L, et al. In vitro anti-HMPV activity of meroditerpenoids from marine alga Stypopodium zonale (Dictyotales). Molecules. 2011;16(10):8437–8450.
  • Pereira DM, Cheel J, Areche C, et al. Anti-Proliferative activity of meroditerpenoids isolated from the brown alga Stypopodium flabelliforme against several cancer cell lines. Mar Drugs. 2011;9(5):852–862.
  • El Hattab M, Genta-Jouve G, Bouzidi N, et al. Cystophloroketals A–E, unusual phloroglucinol-meroterpenoid hybrids from the brown alga Cystoseira tamariscifolia. J Nat Prod. 2015;78(7):1663–1670.
  • Soares AR, Abrantes JL, Souza TML, et al. In vitro antiviral effect of meroditerpenes isolated from the Brazilian seaweed Stypopodium zonale (Dictyotales). Planta Med. 2007;73(11):1221–1224.
  • Valls R, Piovetti L, Banaigst B, et al. Secondary metabolites from Morocco brown algae of the genus Cystoseira. Phytochemistry. 1993;32(4):961–966.
  • Francisco C, Banaigs B, Codomier L, et al. Cystoseirol AA novel rearranged diterpene of mixed biosynthesis from the brown alga Cystoseira mediterranea. Tetrahedron Lett. 1985;26(40):4919–4922.
  • Fadli M, Aracil J-M, Jeanty G, et al. Novel meroterpenoids from Cystoseira mediterranea: use of the crown-gall bioassay as a primary screen for lipophilic antineoplastic agents. J Nat Prod. 1991;54(1):261–264.
  • Amico V, Cunsolo F, Oriente G, et al. Cystoketal, a new metabolite from the brown alga Cystoseira balearica. J Nat Prod. 1984;47(6):947–952.
  • Valls R, Mesguiche V, Piovetti L, et al. Meroditerpenes from the brown alga Cystoseira amentacea var. stricta collected off the French Mediterranean coast. Phytochemistry. 1996;41(5):1367–1371.
  • Vizetto-Duarte C, Custódio L, Acosta G, et al. Can macroalgae provide promising anti-tumoral compounds? A closer look at Cystoseira tamariscifolia as a source for antioxidant and anti-hepatocarcinoma compounds. PeerJ. 2016;4:e1704.
  • Navarro G, Fernández JJ, Norte M. Novel meroditerpenes from the brown alga Cystoseira sp. J Nat Prod. 2004;67(3):495–499.
  • Cho SH, Cho JY, Kang SE, et al. Antioxidant activity of Mojabanchromanol, a novel chromene, isolated from brown alga Sargassum siliquastrum. J Environ Biol. 2008;29(4):479–484.
  • Kikuchi T, Mori Y, Yokoi T, et al. Structure and absolute configuration of sargatriol, a new isoprenoid chromenol from a brown alga, Sargassum tortile C. AGARDH. Chem Pharm Bull. 1983;31(1):106–113.
  • Mokrini R, Mesaoud MB, Daoudi M, et al. Meroditerpenoids and derivatives from the brown alga cystoseira baccata and their antifouling properties. J Nat Prod. 2008;71(11):1806–1811.
  • Menon KVN, Angulo P, Lindor KD. Severe cholestatic hepatitis from troglitazone in a patient with nonalcoholic steatohepatitis and diabetes mellitus. Am J Gastroenterol. 2001;96:1631.
  • Peña-Oyarzun D, Bravo-Sagua R, Diaz-Vega A, et al. Autophagy and oxidative stress in non-communicable diseases: a matter of the inflammatory state? Free radical. Free Radic Biol Med. 2018;124:61–78.
  • Farrokhnia M. Density functional theory studies on the antioxidant mechanism and electronic properties of some bioactive marine meroterpenoids: sargahydroquionic acid and sargachromanol. ACS Omega. 2020;5(32):20382–20390.
  • Kim JA, Ahn BN, Kong CS, et al. The chromene sargachromanol E inhibits ultraviolet a‐induced ageing of skin in human dermal fibroblasts. Br J Dermatol. 2013;168(5):968–976.
  • Kang H-S, Kim J-P. New chromene derivatives with radical scavenging activities from the brown alga Sargassum siliquastrum. Journal of Chemical Research. 2017;41(2):116–119.
  • Bishayee A, Sethi G. Bioactive natural products in cancer prevention and therapy: progress and promise. Semin Cancer Biol. 2016;40–41:1–3.
  • Heo S-J, Kim K-N, Yoon W-J, et al. Chromene induces apoptosis via caspase-3 activation in human leukemia HL-60 cells. Food Chem Toxicol. 2011;49(9):1998–2004.
  • Hur S, Lee H, Kim Y, et al. Sargaquinoic acid and sargachromenol, extracts of Sargassum sagamianum, induce apoptosis in HaCaT cells and mice skin: its potentiation of UVB-induced apoptosis. Eur J Pharmacol. 2008;582(1–3):1–11.
  • Zbakh H, Zubía E, De Los Reyes C, et al. Anticancer activities of meroterpenoids isolated from the brown alga Cystoseira usneoides against the human colon cancer cells HT-29. Foods. 2020;9(3):300.
  • Fernando IPS, Lee WW, Jayawardena TU, et al. 3[β]-hydroxy-[Δ]5-steroidal congeners from a column fraction of Dendronephthya puetteri attenuate LPS-induced inflammatory responses in RAW 264.7 macrophages and zebrafish embryo model. RSC Adv. 2018;8(33):18626–18634.
  • Sah SK, Kim B-H, Park G-T, et al. Novel isonahocol E3 exhibits anti-inflammatory and anti-angiogenic effects in endothelin-1-stimulated human keratinocytes. Eur J Pharmacol. 2013;720(1–3):205–211.
  • Lee J-H, Ko J-Y, Samarakoon K, et al. Preparative isolation of sargachromanol E from Sargassum siliquastrum by centrifugal partition chromatography and its anti-inflammatory activity. Food Chem Toxicol. 2013;62:54–60.
  • Heo S-J, Jang J, Ye B-R, et al. Chromene suppresses the activation of inflammatory mediators in lipopolysaccharide-stimulated RAW 264.7 cells. Food Chem Toxicol. 2014;67:169–175.
  • Yoon W-J, Heo S-J, Han S-C, et al. Anti-inflammatory effect of sargachromanol G isolated from Sargassum siliquastrum in RAW 264.7 cells. Arch Pharm Res. 2012;35(8):1421–1430.
  • Gil B, Ferrándiz ML, Sanz MJ, et al. Inhibition of inflammatory responses by epitaondiol and other marine natural products. Life Sci. 1995;57(2):PL25–PL30.
  • Pérez-Castorena AL, Arciniegas A, Apan MTR, et al. Evaluation of the anti-Inflammatory and antioxidant activities of the plastoquinone derivatives isolated from Roldana barba-johannis. Planta Med. 2002;68(7):645–647.
  • Yang E-J, Ham YM, Yang K-W, et al. Sargachromenol from Sargassum micracanthum inhibits the lipopolysaccharide-induced production of inflammatory mediators in RAW 264.7 macrophages. Sci World J. 2013;2013:1–6.
  • Kim S, Lee M-S, Lee B, et al. Anti-inflammatory effects of sargachromenol-rich ethanolic extract of Myagropsis myagroides on lipopolysaccharide-stimulated BV-2 cells. BMC Complement Altern Med. 2014;14(1):231.
  • Gwon W-G, Joung E-J, Kwon M-S, et al. Sargachromenol protects against vascular inflammation by preventing TNF-α-induced monocyte adhesion to primary endothelial cells via inhibition of NF-κB activation. Int Immunopharmacol. 2017;42:81–89.
  • Joung E-J, Lee B, Gwon W-G, et al. Sargaquinoic acid attenuates inflammatory responses by regulating NF-κB and Nrf2 pathways in lipopolysaccharide-stimulated RAW 264.7 cells. Int Immunopharmacol. 2015;29(2):693–700.
  • Jeong D-H, Kim K-B-W-R, Kim M-J, et al. Anti-inflammatory activity of methanol extract and n-hexane fraction mojabanchromanol b from Myagropsis myagroides. Life Sci. 2014;114(1):12–19.
  • Zbakh H, Zubía E, Reyes C, et al. Meroterpenoids from the brown alga Cystoseira usneoides as potential anti-inflammatory and lung anticancer agents. Mar Drugs. 2020;18(4):207.
  • Kubanek J, Jensen PR, Keifer PA, et al. Seaweed resistance to microbial attack: a targeted chemical defense against marine fungi. Proc Natl Acad Sci USA. 2003;100(12):6916–6921.
  • Chung S-C, Jang KH, Park J, et al. Sargachromanols as inhibitors of Na+/K+ ATPase and isocitrate lyase. Bioorg Med Chem Lett. 2011;21(7):1958–1961.
  • Hayashi K, Mori J, Saito H, et al. Antiviral targets of a chromene derivative from Sargassum micracanthum in the replication of human cytomegalovirus. Biol Pharm Bull. 2006;29(9):1843–1847.
  • Fernando IPS, Ryu B, Ahn G, et al. Therapeutic potential of algal natural products against metabolic syndrome: a review of recent developments. Trends Food Sci Technol. 2020;97:286–299.
  • Rajala MW, Scherer PE. Minireview: the adipocyte-at the crossroads of energy homeostasis, inflammation, and atherosclerosis. Endocrinology. 2003;144(9):3765–3773.
  • Castro M, Preto M, Vasconcelos V, et al. Obesity: the metabolic disease, advances on drug discovery and natural product research. Curr Top Med Chem. 2016;16(23):2577–2604.
  • Sorof J, Daniels S. Obesity hypertension in children: a problem of epidemic proportions. Hypertension. 2002;40(4):441–447.
  • Murugan AC, Karim MR, Yusoff MBM, et al. New insights into seaweed polyphenols on glucose homeostasis. Pharm Biol. 2015;53(8):1087–1097.
  • Park B-G, Shin W-S, Oh S, et al. A novel antihypertension agent, sargachromenol D from marine brown algae, Sargassum siliquastrum, exerts dual action as an L-type Ca2+ channel blocker and endothelin a/B2 receptor antagonist. Bioorg Med Chem. 2017;25(17):4649–4655.
  • Kim S-N, Choi HY, Lee W, et al. Sargaquinoic acid and sargahydroquinoic acid from Sargassum yezoense stimulate adipocyte differentiation through PPARα/γ activation in 3T3-L1 cells. FEBS Lett. 2008;582(23–24):3465–3472.
  • Moon HE, Islam MN, Ahn BR, et al. Protein tyrosine phosphatase 1B and α-glucosidase inhibitory phlorotannins from edible brown algae, Ecklonia stolonifera and Eisenia bicyclis. Biosci Biotechnol Biochem. 2011;75(8):1472–1480.
  • Park B-G, Shin W-S, Um Y, et al. Selective vasodilatation effect of sargahydroquinoic acid, an active constituent of Sargassum micracanthum, on the basilar arteries of rabbits. Bioorg Med Chem Lett. 2008;18(8):2624–2627.
  • Yoon W-J, Heo S-J, Han S-C, et al. Sargachromanol G regulates the expression of osteoclastogenic factors in human osteoblast-like MG-63 cells. Food Chem Toxicol. 2012;50(9):3273–3279.
  • Choi BW, Ryu G, Park SH, et al. Anticholinesterase activity of plastoquinones from Sargassum sagamianum: lead compounds for Alzheimer's disease therapy. Phytother Res. 2007;21(5):423–426.
  • Seong SH, Ali MY, Kim H-R, et al. BACE1 inhibitory activity and molecular docking analysis of meroterpenoids from Sargassum serratifolium. Bioorg Med Chem. 2017;25(15):3964–3970.
  • Tsang CK, Ina A, Goto T, et al. Sargachromenol, a novel nerve growth factor-potentiating substance isolated from Sargassum macrocarpum, promotes neurite outgrowth and survival via distinct signaling pathways in PC12D cells. Neuroscience. 2005;132(3):633–643.
  • Kim J, Ahn BN, Kong CS, et al. Protective effect of chromene isolated from Sargassum horneri against UV-A-induced damage in skin dermal fibroblasts. Exp Dermatol. 2012;21(8):630–631.
  • Tsang CK, Kamei Y. Sargaquinoic acid supports the survival of neuronal PC12D cells in a nerve growth factor-independent manner. Eur J Pharmacol. 2004;488(1–3):11–18.
  • Kamei Y, Tsang CK. Sargaquinoic acid promotes neurite outgrowth via protein kinase a and MAP kinases-mediated signaling pathways in PC12D cells. Int J Dev Neurosci. 2003;21(5):255–262.
  • Afolayan AF, Bolton JJ, Lategan CA, et al. Fucoxanthin, tetraprenylated toluquinone and toluhydroquinone metabolites from Sargassum heterophyllum inhibit the in vitro growth of the malaria parasite Plasmodium falciparum. Z Naturforsch C J Biosci. 2008;63(11–12):848–852.
  • Komai E, Miyahara T, Mori J, et al. Inhibitory activities of plastoquinones and chromene derivative from a brown alga Sagassum micracanthum on bone resorption. Biol Pharm Bull. 2006;29(9):1980–1982.
  • Mori J, Hayashi T, Iwashima M, et al. Effects of plastoquinones from the brown alga Sargassum micracanthum and a new chromene derivative converted from the plastoquinones on acute gastric lesions in rats. Biol Pharm Bull. 2006;29(6):1197–1201.
  • Nimalaratne C, Sun C, Wu J, et al. Quantification of selected fat soluble vitamins and carotenoids in infant formula and dietary supplements using fast liquid chromatography coupled with tandem mass spectrometry. Food Res Int. 2014;66:69–77.
  • Górnaś P, Šnē E, Siger A, et al. Sea buckthorn (Hippophae rhamnoides L.) leaves as valuable source of lipophilic antioxidants: the effect of harvest time, sex, drying and extraction methods. Ind Crops Prod. 2014;60:1–7.
  • Lim H, Woo S, Kim HS, et al. Comparison of extraction methods for determining tocopherols in soybeans. Eur J Lipid Sci Technol. 2007;109(11):1124–1127.
  • Galli F, Lee R, Dunster C, et al. Gas chromatography mass spectrometry analysis of carboxyethyl-hydroxychroman metabolites of α- and γ-tocopherol in human plasma. Free Radic Biol Med. 2002;32(4):333–340.
  • Zhao Y, Lee M-J, Cheung C, et al. Analysis of multiple metabolites of tocopherols and tocotrienols in mice and humans. J Agric Food Chem. 2010;58(8):4844–4852.
  • Grebenstein N, Frank J. Rapid baseline-separation of all eight tocopherols and tocotrienols by reversed-phase liquid-chromatography with a solid-core pentafluorophenyl column and their sensitive quantification in plasma and liver. J Chromatogr A. 2012;1243:39–46.
  • Guthrie N, Gapor A, Chambers AF, et al. Inhibition of proliferation of estrogen receptor-negative MDA-MB-435 and -positive MCF-7 human breast cancer cells by palm oil tocotrienols and tamoxifen, alone and in combination. J Nutr. 1997;127(3):544S–548S.
  • Zarrouk W, Carrasco-Pancorbo A, Zarrouk M, et al. Multi-component analysis (sterols, tocopherols and triterpenic dialcohols) of the unsaponifiable fraction of vegetable oils by liquid chromatography-atmospheric pressure chemical ionization-ion trap mass spectrometry. Talanta. 2009;80(2):924–934.
  • Shen B. A new golden age of natural products drug discovery. Cell. 2015;163(6):1297–1300.
  • Li JWH, Vederas JC. Drug discovery and natural products: end of an era or an endless frontier? Science. 2009;325(5937):161–165.
  • Molinski TF, Dalisay DS, Lievens SL, et al. Drug development from marine natural products. Nat Rev Drug Discov. 2009;8(1):69–85.
  • Bouslimani A, Sanchez LM, Garg N, et al. Mass spectrometry of natural products: current, emerging and future technologies. Nat Prod Rep. 2014;31(6):718–729.
  • Rudolf JD, Yan X, Shen B. Genome neighborhood network reveals insights into enediyne biosynthesis and facilitates prediction and prioritization for discovery. J Ind Microbiol Biotechnol. 2016;43(2–3):261–276.

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