- A regiospecific rhamnosyltransferase from: Epimedium pseudowushanense catalyzes the 3- O -rhamnosylation of prenylflavonols
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Epimedium is used in traditional Chinese medicine and contains flavonol glycosides that exhibit multiple biological activities. These bioactive flavonol glycosides usually have a rhamnose moiety at the 3-OH position of prenylflavonols, such as icariin (9), baohuoside I (1a) and baohuoside II (2a). However, to date, no rhamnosyltransferase has been reported to catalyze the 3-O-rhamnosylation of prenylflavonols. In this article, a flavonol rhamnosyltransferase, EpPF3RT, was identified from E. pseudowushanense B. L. Guo. The recombinant enzyme regiospecifically transfers a rhamnose moiety to 8-prenylkaempferol (1) and anhydroicaritin (2) at the 3-OH position to form baohuoside II (1a) and baohuoside I (2a) in vitro. In addition, a UDP-rhamnose synthase gene, EpRhS, from E. pseudowushanense was functionally characterized and used to produce the UDP-rhamnose sugar donor. Furthermore, an engineered Escherichia coli strain containing EpPF3RT and EpRhS was established to produce baohuoside II (1a) from whole cells. These studies indicate the significant potential of an enzymatic approach for the rhamnosylation of bioactive flavonoids in Epimedium plants and will provide a promising alternative for producing bioactive rhamnosylated flavonoids combined with other genes/enzymes by synthetic biology.
- Feng, Keping,Chen, Ridao,Xie, Kebo,Chen, Dawei,Guo, Baolin,Liu, Xiao,Liu, Jimei,Zhang, Min,Dai, Jungui
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p. 452 - 458
(2018/02/06)
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- Studies on α-glucosidase, aldose reductase and glycation inhibitory properties of sesquiterpenes and flavonoids of Zingiber zerumbet Smith
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Eight known phytochemicals, four sesquiterpenes and four flavonoids of Zingiber zerumbet were screened against α-glucosidase enzyme, aldose reductase enzyme and antiglycation property under in vitro conditions. The results established kaempferol-3-O-methylether as a potent inhibitor of α-glucosidase enzyme with an IC50 value of 7.88 M. In aldose reductase enzyme inhibition assay, all the compounds except zerumbone epoxide showed good to excellent inhibition properties. Among these, the flavonoid compounds were found to be potent aldose reductase inhibitors compared with the four sesquiterpenes. In addition, compounds such as α-humulene, kaempferol, kaempferol-3-O-methylether and 3″,4″-O-diacetylafzelin displayed potent antiglycation properties. From overall results, we found that kaempferol and kaempferol-3-O-methylether are potent inhibitors of α-glucosidase enzyme, aldose reductase enzyme and glycation reaction, the three main targets of drugs for the treatment of diabetes and its complications.
- Ajish,Antu,Riya,Preetharani,Raghu,Dhanya,Radhakrishnan
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supporting information
p. 947 - 952
(2015/05/13)
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- The Gastrointestinal Tract Metabolism and Pharmacological Activities of Grosvenorine, a Major and Characteristic Flavonoid in the Fruits of Siraitia grosvenorii
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Grosvenorine is the major flavonoid compound of the fruits of Siraitia grosvenorii (Swingle) C. Jeffrey, a medical plant endemic to China. In the present study, for the first time, the grosvenorine metabolism in an in vitro simulated human gastrointestinal tract (including artificial gastric juice, artificial intestinal juice and intestinal flora), as well as its pharmacological activities (including anti-complement, antibacterial and antioxidant activities), was investigated. The results showed that grosvenorine was metabolized by human intestinal flora; its four metabolites were isolated by semi-preparative HPLC and identified by NMR as kaempferitrin, afzelin, α-rhamnoisorobin, and kaempferol. Further pharmacological evaluation showed that grosvenorine exhibited good antibacterial and antioxidant activities, with its metabolites possessing more potent activities. Although grosvenorine did not present obvious anticomplement activity, its metabolites showed interesting activities. This study revealed that intestinal bacteria play an important role in the gastrointestinal metabolism of grosvenorine and significantly affect its pharmacological activities.
- Wang, Mengyue,Xing, Shihua,Luu, Thithanhthuy,Fan, Min,Li, Xiaobo
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p. 1652 - 1664
(2015/11/24)
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- Changes in flavonoid content and tyrosinase inhibitory activity in kenaf leaf extract after far-infrared treatment
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The tyrosinase inhibitory activity of ethanolic extract of kenaf (Hibiscus cannabinus L.) leaf was evaluated before and after subjecting it to far-infrared (FIR) irradiation. The main component of the extract was analyzed as kaempferitrin (kaempferol-3,7-O-α-dirhamnoside). Prior to FIR irradiation, no inhibitory activity of the extract was detected in a tyrosinase assay. However, after FIR irradiation for 1 h at 60 °C, significant tyrosinase inhibitory activity (IC50 = 3500 ppm) was observed in it. In HPLC analysis, derhamnosylation products (kaempferol, afzelin, and α-rhamnoisorobin) were detected. The inhibitory activity may be due to the existence of derhamnosylation products. This study demonstrated that FIR irradiation can be used as a convenient tool for deglycosylation of flavonoid glycoside.
- Rho, Ho Sik,Ahn, Soo Mi,Lee, Bum Chun,Kim, Myung Kyoo,Ghimeray, Amal Kumar,Jin, Cheng Wu,Cho, Dong Ha
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scheme or table
p. 7534 - 7536
(2011/02/24)
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- Structural basis for the activity of the RSK-specific inhibitor, SL0101
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Inappropriate activity of p90 ribosomal S6 kinase (RSK) has been implicated in various human cancers as well as other pathologies. We previously reported the isolation, characterization, and synthesis of the natural product kaempferol 3-O-(3″,4″-di-O-acetyl-α-l-rhamnopyranoside), termed SL0101 [Smith, J. A.; Poteet-Smith, C. E.; Xu, Y.; Errington, T. M.; Hecht, S. M.; Lannigan, D. A. Cancer Res., 2005, 65, 1027-1034: Xu, Y.-M; Smith, J. A.; Lannigan, D. A.; Hecht, S. M. Bioorg. Med. Chem., 2006, 14, 3974-3977: Maloney, D. J.; Hecht, S. M. Org. Lett., 2005, 7, 1097-1099]. SL0101 is a potent and specific inhibitor of RSK; therefore, we performed an analysis of the structural basis for the inhibitory activity of this lead compound. In in vitro kinase assays we found that acylation of the rhamnose moiety and the 4′, 5, and 7-hydroxyl groups are responsible for maintaining a high affinity interaction of RSK with SL0101. It is likely that the hydroxyl groups facilitate RSK binding through their ability to form hydrogen bonds. To determine whether the SL0101 derivatives were specific for inhibition of RSK we analyzed their ability to preferentially inhibit the growth of the human breast cancer line, MCF-7, compared to the normal human breast line, MCF-10A. We have previously validated this differential growth assay as a convenient readout for analyzing the specificity of RSK inhibitors [Smith, J. A.; Maloney, D. J.; Clark, D. E.; Xu, Y.-M.; Hecht, S. M.; Lannigan, D. A. Bioorg. Med. Chem., 2006, 14, 6034-6042]. We found that acylation of the rhamnose moiety was essential for maintaining the selectivity for RSK inhibition in intact cells. Further, the efficacy of SL0101 in intact cells is limited by cellular uptake as well as possible hydrolysis of the acetyl groups on the rhamnose moiety by ubiquitous intracellular esterases. These studies should facilitate the development of a RSK inhibitor, based on the SL0101 pharmacophore, as an anti-cancer chemotherapeutic agent.
- Smith, Jeffrey A.,Maloney, David J.,Hecht, Sidney M.,Lannigan, Deborah A.
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p. 5018 - 5034
(2008/03/12)
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- De novo asymmetric syntheses of SL0101 and its analogues via a palladium-catalyzed glycosylation
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(Chemical Equation Presented) The enantioselective syntheses of naturally occurring kaempferol glycoside SL0101 (1a) and its analogues 1b-e, as well as their enantiomers, have been achieved in 7-10 steps. The routes rely upon a diastereoselective palladium-catalyzed glycosylation, ketone reduction, and dihydroxylation to introduce the rhamno-stereochemistry. The asymmetry of the sugar moiety of these kaempferol glycosides was derived from Noyori reduction of an acylfuran. An acetyl group shift from an axial (C-2) to equatorial position (C-3) under basic conditions was also described.
- Shan, Mingde,O'Doherty, George A.
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p. 5149 - 5152
(2007/10/03)
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- Flavonol glycosides from Cassia hirsuta
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A new flavonol glycoside, kaempferol 3-O-α-L-rhamnopyranosyl (1→2)- α-L-rhamnopyranoside (1), was isolated from the flowers of Cassia hirsuta along with two known flavonol glycosides, kaempferol 3-O-rutinoside and rutin. The structure of compound 1 has been established on the basis of spectral data and by acid hydrolysis.
- Rao,Damu,Jayaprakasam,Gunasekar
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p. 305 - 306
(2007/10/03)
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- Flavonoid Constituents of Zingiber zerumbet Smith
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Two flavonoid glycosides (6 and 7) and two flavonols (3 and 4) were isolated from the CH2Cl2-soluble part of the extract of fresh rhizomes of Zingiber zerumbet Smith, along with zerumbone (1), zerumbone epoxide (2) and curcumin (5).The structures of the isolated compounds were determined to be kaempferol-3,4'-O-dimethylether (3), kaempferol-3-O-methylether (4), kaempferol-3-O-(3,4-O-diacetyl-α-L-rhamnopyranoside) (6) and kaempferol-3-O-(2,4-O-diacetyl-α-L-rhamnopyranoside) (7).The stability of the two flavonoid glycosides (6 and 7) and their occurrence in the fresh rhizome are also discussed.
- Nakatani, Nobuji,Jitoe, Akiko,Masuda, Toshiya,Yonemori, Shigetomo
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p. 455 - 460
(2007/10/02)
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- TWO FLAVONOL GLYCOSIDES FROM CHENOPODIUM AMBROSIOIDES
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Two new flavonol glycosides, kaempferol 3-rhamnoside-4'-xyloside and kaempferol 3-rhamnoside-7-xyloside along with kaempferol, isorhamnetin and quercetin have been identified from the fruits of Chenopodium ambrosioides.Their structures were established using spectroscopic and chemical evidence.
- Jain, Neeru,Alam, M. Sarwar,Kamil, M.,Ilyas, M.,Niwa, M.,Sakae, A.
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p. 3988 - 3991
(2007/10/02)
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- FOUR KAEMPFEROL GLYCOSIDES FROM LEAVES OF CINNAMOMUM SIEBOLDII
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Four flavonol glycosides were isolated from Cinnamomum sieboldii and characterized as kaempferol 7-O-α-L-rhamnopyranosides having 3-O-α-L-rhamnopyranosyl, 3-O-α-L-arabinofuranosyl, 3-O-β-D-apiofuranosyl-(1-->2)-α-L-arabinofuranosyl and 3-O-β-D-glucopyranosyl-(1-->3)-α-L-rhamnopyranosyl residues, respectively.The latter three are new compounds. - Key Word Index: Cinnamomum sieboldii; Lauraceae; leaves; flavonoids; kaempferol glycosides.
- Nakano, Kimiko,Takatani, Mikiko,Tomimatsu, Toshiaki,Nohara, Toshihiro
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p. 2831 - 2834
(2007/10/02)
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