Flazin

A new flavonol acylglycoside from the fruits of Nitraria tangutorum Bobr.[Pubmed:32011162]

Nat Prod Res. 2020 Feb 3:1-6.

Phytochemical investigation on the ethanol extract of the fruits of Nitraria tangutorum Bobr. led to the isolation of a new flavonol acylglycoside tangutoside (7) and six known ones including p-formylphenol (1), 3-formylindole (2), rutin (3), prionitisid B (4), quercitrin (5) and Flazin (6). Among them, compounds 2, 4, and 5 were isolated from Nitraria tangutorum Bobr. for the first time. Their structures were identified by spectroscopic methods and by comparison with data reported in the references. The compounds 3, 4, 5, and 7 were demonstrated to possess strong DPPH radical scavenging ability with IC50 values of 31.45 mug/mL, 19.21 mug/mL, 59.30 mug/mL, and 44.54 mug/mL, respectively.

Flazin as a Promising Nrf2 Pathway Activator.[Pubmed:31668063]

J Agric Food Chem. 2019 Nov 20;67(46):12844-12853.

Flazin is a beta-carboline-derived alkaloid found in Japanese fermented foods. Here, the potential of Flazin as an antioxidant food was studied with particular reference to its effect on the Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) system in human hepatocytes (C3A). Flazin and Flazin analogues including the decarboxylated derivative perlolyrine were chemically synthesized and compared with each other and with chlorogenic acid and curcumin. Among these compounds, Flazin showed the lowest cytotoxicity (IC50 < 500 muM) and the highest capacity to activate the Keap1-Nrf2 system. It provided the largest (>3-fold of the control) cytoprotection ability against a pro-oxidant, although its radical absorbance capacity was relatively low. Flazin increased the expressions of Nrf2-dependent phase II enzyme genes and their products (NQO1, GSTP, and GSH proteins). The strong cytoprotection ability of Flazin associated with low logP (0-3) is shared by sulforaphane and 3,5-dihydroxy-4-methoxybenzyl alcohol, suggesting the potential value of Flazin and Flazin-rich foods for the prevention of oxidation-related health disorders.

Effect of Soy Sauce on Serum Uric Acid Levels in Hyperuricemic Rats and Identification of Flazin as a Potent Xanthine Oxidase Inhibitor.[Pubmed:27181598]

J Agric Food Chem. 2016 Jun 15;64(23):4725-34.

This is the first report on the ability of soy sauce to effectively reduce the serum uric acid levels and xanthine oxidase (XOD) activities of hyperuricemic rats. Soy sauce was partitioned sequentially into ethyl acetate and water fractions. The ethyl acetate fraction with strong XOD inhibition effect was purified further. On the basis of xanthine oxidase inhibitory (XOI) activity-guided purification, nine compounds including 3,4-dihydroxy ethyl cinnamate, diisobutyl terephthalate, harman, daidzein, Flazin, catechol, thymine, genistein, and uracil were obtained. It was the first time that 3,4-dihydroxy ethyl cinnamate and diisobutyl terephthalate had been identified from soy sauce. Flazin with hydroxymethyl furan ketone group at C-1 and carboxyl at C-3 exhibited the strongest XOI activity (IC50 = 0.51 +/- 0.05 mM). According to fluorescence quenching and molecular docking experiments, Flazin could enter into the catalytic center of XOD to interact with Lys1045, Gln1194, and Arg912 mainly by hydrophobic forces and hydrogen bonds. Flazin, catechol, and genistein not only were potent XOD inhibitors but also held certain antioxidant activities. According to ADME (absorption, distribution, metabolism, and excretion) simulation in silico, Flazin had good oral bioavailability in vivo.

[Chemical constituents from Paris mairei].[Pubmed:25509296]

Zhongguo Zhong Yao Za Zhi. 2014 Aug;39(16):3107-11.

Twelve compounds were isolated from the rhizome of Paris mairei Levl by silica gel, Sephadex LH-20 and ODS col-umn chromatographies. The structure elucidation was accomplished by ESI-MS and NMR methods. These compounds were identified as lupeol(1), lup-20(29) -ene-3beta-yl octacosanoate(2), palmitic acid(3), glyceryl alpha-mono-palmitate(4), alpha-spinasterol(5), diosgenin (6), (25R) diosgenin-3-O-alpha-L-rhamnopyranosyl (1--> 4) -alpha-L-rhamnopyranosyl (1 --> 4) - [alpha-L-rhamnopyranosyl(1 --> 2)] -beta-D-glucopyranoside(7), pennogenin(8), pennogenin-3-O-beta-D-glucopyranosyl(1 -->3) - [alpha-L-rhamnopyranosyl(1 --> 2)] -beta-D-glucopyranoside(9), Flazin(10), calonysterone(11), and isorhamnetin-3-O-beta-gentiobioside(12). Compounds 1-5,10-11 were isolated from the genus Paris for the first time, and all compounds were isolated from this plant for the first time.

Alkaloids from the mangrove-derived actinomycete Jishengella endophytica 161111.[Pubmed:24451190]

Mar Drugs. 2014 Jan 21;12(1):477-90.

A new alkaloid, 2-(furan-2-yl)-6-(2S,3S,4-trihydroxybutyl)pyrazine (1), along with 12 known compounds, 2-(furan-2-yl)-5-(2S,3S,4-trihydroxybutyl)pyrazine (2), (S)-4-isobutyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde (3), (S)-4-isopropyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde (4), (4S)-4-(2-methylbutyl)-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbalde hyde (5), (S)-4-benzyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde (6), Flazin (7), perlolyrine (8), 1-hydroxy-beta-carboline (9), lumichrome (10), 1H-indole-3-carboxaldehyde (11), 2-hydroxy-1-(1H-indol-3-yl)ethanone (12), and 5-(methoxymethyl)-1H-pyrrole-2-carbaldehyde (13), were isolated and identified from the fermentation broth of an endophytic actinomycetes, Jishengella endophytica 161111. The new structure 1 and the absolute configurations of 2-6 were determined by spectroscopic methods, J-based configuration analysis (JBCA) method, lactone sector rule, and electronic circular dichroism (ECD) calculations. Compounds 8-11 were active against the influenza A virus subtype H1N1 with IC50 and selectivity index (SI) values of 38.3(+/-1.2)/25.0(+/-3.6)/39.7(+/-5.6)/45.9(+/-2.1) mug/mL and 3.0/16.1/3.1/11.4, respectively. The IC50 and SI values of positive control, ribavirin, were 23.1(+/-1.7) mug/mL and 32.2, respectively. The results showed that compound 9 could be a promising new hit for anti-H1N1 drugs. The absolute configurations of 2-5, 13C nuclear magnetic resonance (NMR) data and the specific rotations of 3-6 were also reported here for the first time.

beta-carboline derivatives and diphenols from soy sauce are in vitro quinone reductase (QR) inducers.[Pubmed:21332190]

J Agric Food Chem. 2011 Mar 23;59(6):2332-40.

A murine hepatoma (Hepa 1c1c7) cellular bioassay was used to guide the isolation of phase II enzyme inducers from fermented soy sauce, using quinone reductase (QR) as a biomarker. A crude ethyl acetate extract, accounting for 8.7% of nonsalt soluble solids of soy sauce, was found to double relative QR specific activity at 25 mug/mL (concentration required to double was defined as a "CD value"). Further silica gel column fractionation yielded 17 fractions, 16 of which exhibited CD values for QR induction of <100 mug/mL. The four most potent fractions were subfractionated by column and preparative thin layer chromatography, leading to the isolation and identification of two phenolic compounds (catechol and daidzein) and two beta-carbolines (Flazin and perlolyrin), with respective CD values of 8, 35, 42, and 2 muM. Western blots confirmed that the increases in QR activity corresponded to dose-dependent increases in cellular levels of NAD[P]H:quinone oxidoreductase 1 protein by these four QR inducers. To the authors' knowledge, this is the first report on the ability of beta-carboline-derived alkaloids to induce phase II enzymes.

Synthesis of analogues of flazin, in particular, flazinamide, as promising anti-HIV agents.[Pubmed:18357553]

Chem Biodivers. 2008 Mar;5(3):447-60.

Flazin isolated from the fruiting bodies of Suillus granulatus was found to possess weak anti-HIV activity (EC(50)=2.36 microM, TI=12.1). To establish a SAR study, 46 Flazin analogues were synthesized, and their anti-HIV activities were evaluated in vitro. Among them, Flazinamide (9a) showed the most potent activity with an EC(50) value of 0.38 microM and a TI value of 312.0. The results suggested that appropriate substituents at positions 3, 1', and 5' of Flazin might play a crucial role in determining their anti-HIV activities, and that Flazinamide can be considered as a promising, readily available anti-HIV agent.

[Studies on chemical constituents from roots of Mirabilis jalapa].[Pubmed:18338618]

Zhongguo Zhong Yao Za Zhi. 2008 Jan;33(1):42-6.

OBJECTIVE: To investigate the anti-HIV constituents from the root of Mirabilis jalapa. METHOD: The compounds were isolated by column chromatography on silica gel, Sephadex LH - 20, MCI-gel CHP-20P and RP-18. The structure were identified by means of NMR and MS analyses (1H-NMR, 13C-NMR, MS). RESULT: Eleven compounds were isolated and identified as astragaloside II (1), astragaloside II (2), astragaloside IV (3), astragaloside VI (4), Flazin (5), 4'-hydroxy-2, 3-dihydroflavone 7-beta-D-glucopyranoside (6), gingerglycolipid A (7), 3, 4-dihydroxybenzaldehyd (8), p-hydroxybenzaldehyde (9), beta-sitosterol (10) and daucosterol (11). CONCLUSION: Compounds 1-9 were obtained from this genus for the first time.

Flazinamide, a novel beta-carboline compound with anti-HIV actions.[Pubmed:17336271]

Biochem Biophys Res Commun. 2007 Apr 20;355(4):1091-5.

A beta-carboline compound, Flazin isolated from Suillus granulatus has been shown weak anti-HIV-1 activity. Based on the structure of Flazin, Flazinamide [1-(5'- hydromethyl-2'-furyl)-beta-carboline-3-carboxamide] was synthesized and its anti-HIV activities were evaluated in the present study. The cytotoxicity of Flazinamide was about 4.1-fold lower than that of Flazin. Flazinamide potently reduced syncytium formation induced by HIV-1IIIB with EC50 value of 0.38muM, the EC50 of Flazinamide was about 6.2-fold lower than that of Flazin. Flazinamide also inhibited HIV-2ROD and HIV-2CBL-20 infection with EC50 values of 0.57 and 0.89microM, respectively. Flazinamide reduced p24 antigen expression in HIV-1IIIB acute infected C8166 and in clinical isolated strain HIV-1KM018 infected PBMC, with EC50 values of 1.45 and 0.77microM, respectively. Flazinamide did not suppress HIV-1 replication in chronically infected H9 cells. Flazinamide blocked the fusion between normal cells and HIV-1 or HIV-2 chronically infected cells. It weakly inhibited activities of recombinant HIV-1 reverse transcriptase, protease or integrase at higher concentrations. In conclusion, the conversion of the carboxyl group in 3 position of Flazin markedly enhanced the anti-viral activity (TI value increased from 12.1 to 312.2) and Flazinamide might interfere in the early stage of HIV life cycle.

A new antibiotic, antimycin Ag, produced by Streptomyces sp. K01-0031.[Pubmed:15813185]

J Antibiot (Tokyo). 2005 Jan;58(1):74-8.

A new antimycin group antibiotic, antimycin A9, was isolated from a cultured broth of Streptomyces sp. K01-0031 together with antimycins A3a, A3b, A4, and A7, and Flazin methyl ester. Antimycin A9 is the first antimycin having an aromatic 8-acyl residue. It showed potent nematocidal and insecticidal activities against Caenorhabditis elegans and Artemia salina, respectively. It inhibited bovine heart NADH oxidase at nanomolar level like other known antimycins.

Bioactive constituents of the seeds of Brucea javanica.[Pubmed:12221597]

Planta Med. 2002 Aug;68(8):730-3.

A new quassinoid, yadanziolide S (1), was isolated from the seeds of the traditional Chinese medicinal herb, Brucea javanica, along with ten known compounds, Flazin, bruceine D, yadanziolide B, bruceoside A, yadanziolide S, yadanzigan, glycerol 1,3-bisoleate, azelaic acid, (+/-)-8-hydroxyhexadecanoic acid, and vanillin. Compound 1 is the first quassinoid to have been isolated from B. javanica without a methyleneoxy bridge between C-8 and C-13, and its structure was determined using spectroscopic methods, and confirmed by single-crystal X-ray diffraction. All isolates were evaluated for their potential to induce human promyelocytic leukemia (HL-60) cell differentiation, and to inhibit cyclooxygenase-1 (COX-1), -2 (COX-2), and 7,12-dimethylbenz[a]anthracene (DMBA)-induced lesions in a mouse mammary organ culture model.