Bioconversion of 7-Hydroxyflavanone: Isolation, Characterization and Bioactivity Evaluation of Twenty-One Phase I and Phase II Microbial Metabolites

Microbial metabolism of 7-hydroxyflavanone (1) with fungal culture Cunninghamella blakesleeana (ATCC 8688a), yielded flavanone 7-sulfate (2), 7,4'-dihydroxyflavanone (3), 6,7-dihydroxyflavanone (4), 6-hydroxyflavanone 7-sulfate (5), and 7-hydroxyflavanone 6-sulfate (6). Mortierella zonata (ATCC 13309) also transformed 1 to metabolites 2 and 3 as well as 4'-hydroxyflavanone 7-sulfate (7), flavan-4-cis-ol 7-sulfate (8), 2',4'-dihydroxychalcone (9), 7,8-dihydroxyflavanone (10), 8-hydroxyflavanone 7-sulfate (11), and 8-methoxy-7-hydroxyflavanone (12). Beauveria bassiana (ATCC 7159) metabolized 1 to 2, 3, and 8, flavanone 7-O-β-D-O-4-methoxyglucopyranoside (13), and 8-hydroxyflavanone 7-O-β-D-O-4-methoxyglucopyranoside (14). Chaetomium cochlioides (ATCC 10195) also transformed 1 to 2, 3, 9, together with 7-hydroxy-4-cis-ol (15). Mucor ramannianus (ATCC 9628) metabolized 1 in addition to 7, to also 4,2',4'-trihydroxychalcone (16), 7,3',4'-trihydroxyflavanone (17), 4'-hydroxyflavanone 7-O-α-L-rhamnopyranoside (18), and 7,3',4'-trihydroxy-6-methoxyflavanone (19). The organism Aspergillus alliaceus (ATCC 10060) transformed 1 to metabolites 3, 16, 7,8,4'-trihydroxyflavanone (20), and 7-hydroxyflavanone 4'-sulfate (21). A metabolite of 1, flavanone 7-O-β-D-O-glucopyranoside (22) was produced by Rhizopus oryzae (ATCC 11145). Structures of the metabolic products were elucidated by means of spectroscopic data. None of the metabolites tested showed antibacterial, antifungal and antimalarial activities against selected organisms. Metabolites 4 and 16 showed weak antileishmanial activity.     

Optical isomer separation of flavanones and flavanone glycosides by nano-liquid chromatography using a phenyl-carbamate-propyl-β-cyclodextrin chiral stationary phase

In this paper a phenyl-carbamate-propyl-β-cyclodextrin stationary phase was employed for the enantioseparation of several flavonoids, including flavanones and methoxyflavanones by using nano-liquid chromatography (nano-LC). The same stationary phase was also used for the diastereoisomeric separation of two flavanone glycosides. The compounds: flavanone, 2′-hydroxyflavanone, 4′-hydroxyflavanone, 6-hydroxyflavanone, 7-hydroxyflavanone, 4′-methoxyflavanone, 6-methoxyflavanone, 7-methoxyflavanone, hesperetin, hesperidin, naringenin and naringin were studied using reversed, polar organic and normal elution modes. The effect of the nature and composition of the mobile phase (organic modifier type, buffer and water content in the reversed phase mode) on the enantioresolution (R_s), retention factor (k) and enantioselectivity (α) were investigated. Baseline resolution of all studied flavonoids, with the exception of 2′-hydroxyflavanone and naringin, was achieved in reversed phase mode using a mixture of MeOH/H₂O at different ratios as mobile phase. Good results, in terms of peak efficiency and short analysis time, were obtained adding 1% triethylammonium acetate pH 4.5 buffer to MeOH/H₂O mixture. The separation of the studied compounds was also performed in polar organic mode. By using 100% of MeOH as mobile phase, the resolution was achieved for the studied analytes, except for 7-hydroxyflavanone, 2′-hydroxyflavanone, naringenin, hesperidin and naringin. Normal mode was tested employing a mixture of EtOH/hexane/TFA as mobile phase achieving the enantiomeric and diastereomeric separation of only hesperetin and hesperidin, respectively. The use of nano-LC technique for the resolution of flavanones optical isomers allowed to achieve good resolutions in shorter analysis time compared to the results reported in literature with conventional HPLC.     

Synthesis of 1-[(3-Halo-1-Hydroxy-2-Propoxy)methyl]uracil and Thymine as Potential Antiviral Agents

3′-Halogen acyclonucleoside analogs have been prepared. The starting material, benzyl glycidyl ether (5) , prepared from eplchlorohydrin and sodium benzyloxidc, underwent ring opening by soft halogen ions to give l-benzyloxy-3-fluoro-2-propanol (6) , l-bcnzyloxy-3-chloro-2-propanol (7) , and l-benzyloxy-3- bromo-2-propanol (8) respectively. The treatment of 5 with lithium iodide in the presence of acetic acid provided 1-benzyloxy-3-iodo-2-propanol (9) . The treatment of 8 with sodium iodide in anhydrous acetone also produced l-benzyloxy-3-iodo-2-propanol (9) . Chloromethylation of these halohydrins 6-9 using paraformaldehyde and hydrogen chloride gas produced the chloromcthyl ethers 10-13 . These chloromethyl ethers without further purification were allowed to react with the silylated bases 16-17 , previously prepared by silylating the bases 14-15 with HMDS in the presence of ammonium sulfate to give 1- [(l-benzyloxy-3-halogen-2-propoxy)methyl]uracils and thymines 19-25 . The target compounds 26-33 were obtained respectively after the debcnzylation of 18-25 . Compounds 26, 27, 30 and 31 had no significant cell toxicity in the range of concentrations 0.001-20 mM. Compounds 26, 27, 28 and 29 have no significant activity against HSV II (for less than 2 mM there is a cytopathic effect). Compounds 30, 31, 32 and 33 show no activity against HSV II virus even at the level 20 mM.     

Synthesis and 5α-reductase inhibitory activity of C₂₁ steroids having 1,4-diene or 4,6-diene 20-ones and 4-azasteroid 20-oximes

The synthesis and evaluation of 5α-reductase inhibitory activity of some 4-azasteroid-20-ones and 20-oximes and 3β-hydroxy-, 3β-acetoxy-, or epoxy-substituted C?? steroidal 20-ones and 20-oximes having double bonds in the A and/or B ring are described. Inhibitory activity of synthesized compounds was assessed using 5α-reductase enzyme and [1,2,6,7-3H]testosterone as substrate. All synthesized compounds were less active than finasteride (IC??: 1.2 nM). Three 4-azasteroid-2-oximes (compounds 4, 6 and 8) showed good inhibitory activity (IC??: 26, 10 and 11 nM) and were more active than corresponding 4-azasteroid 20-ones (compounds 3, 5 and 7). 3β-Hydroxy-, 3β-acetoxy- and 1α,2α-, 5α,6α- or 6α,7α-epoxysteroid-20-one and -20-oxime derivatives having double bonds in the A and/or B ring showed no inhibition of 5α-reductase enzyme.     

Prolyl endopeptidase inhibitors from the underground part of Rhodiola sachalinensis

The methanolic extract of the underground part of Rhodiola sachalinensis was found to show inhibitory activity on prolyl endopeptidase (PEP, EC. 3.4.21.26), an enzyme that plays a role in the metabolism of proline-containing neuropeptidase which is recognized to be involved in learning and memory. From the MeOH extract, five new monoterpenoids named sachalinols A (24), B (25) and C (26) and sachalinosides A (23) and B (27) were isolated, together with twenty-two known compounds, gallic acid (1), trans-p-hydroxycinnamic acid (2), p-tyrosol (3), salidroside (4), 6n-O-galloylsalidroside (5), benzyl beta-D-glucopyranoside (6), 2-phenylethyl beta-D-glucopyranoside (7), trans-cinnamyl beta-D-glucopyranoside (8), rosarin (9), rhodiocyanoside A (10), lotaustralin (11), octyl beta-D-glucopyranoside (12), 1,2,3,6-tetra-O-galloyl-beta-D-glucose (13), 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (14), kaempferol (15), kaempferol 3-O-beta-D-xylofuranosyl(1-->2)-beta-D-glucopyranoside (16), kaempferol 3-O-beta-D-glucopyranosyl(1-->2)-beta-D-glucopyranoside (17), rhodionin (18), rhodiosin (19), (-)-epigallocatechin (20), 3-O-galloylepigallocatechin-(4-->8)-epigallocatechin 3-O-gallate (21) and rosiridin (22). Among these, nineteen compounds other than 3, 4 and 9 have been isolated for the first time from R. sachalinensis, and six (6, 8, 13, 16, 17, 20) are isolated from Rhodiola plants for the first time. Among them, six compounds (13, 14, 18, 19, 21, 22) showed noncompetitive inhibition against Flavobacterium PEP, with an IC50 of 0.025, 0.17, 22, 41, 0.44 and 84 microM, respectively.     

Evaluation of novel amylose and cellulose-based chiral stationary phases for the stereoisomer separation of flavanones by means of nano-liquid chromatography

Three polysaccharide-based chiral stationary phases, Sepapak^® 1, Sepapak^® 2 and Sepapak^® 3 have been evaluated in the present work for the stereoisomer separation of a group of 12 flavonoids including flavanones (flavanone, 4′-methoxyflavanone, 6-methoxyflavanone, 7-methoxyflavanone, 2′-hydroxyflavanone, 4′-hydroxyflavanone, 6-hydroxyflavanone, 7-hydroxyflavanone, hesperetin, naringenin) and flavanone glycosides (hesperidin, naringin) by nano-liquid chromatography (nano-LC). The behaviour of these chiral stationary phases (CSPs) towards the selected compounds was studied in capillary columns (100 μm internal diameter (i.d.)) packed with the above mentioned CSPs using polar organic, reversed and normal elution modes. The influence of nature and composition of the mobile phase in terms of concentration and type of organic modifier, buffer type and water content (reversed phase elution mode) on the enantioresolution (R_s), retention factor (k) and enantioselectivity (α) was evaluated. Sepapak^® 3 showed the best chromatographic results in terms of enantioresolution, enantioselectivity and short analysis time, employing a polar organic phase mode. A mixture of methanol/isopropanol (20/80, v/v) as mobile phase enabled the chiral separation of eight flavanones with enantioresolution factor (R_s) in the range 1.15–4.18. The same analytes were also resolved employing reversed and normal phase modes with mixtures of methanol/water and hexane/ethanol at different ratios as mobile phases, respectively. Loss in resolution for some compounds, broaden peaks and longer analysis times were observed with these last two chromatographic elution modes.     

New polyhydroxylated furostanol saponins with inhibitory action against NO production from Tupistra chinensis rhizomes

Two furostanol saponins were obtained from the rhizomes of Tupistra chinensis Bak. Their structures were determined as 5beta-furost-delta(25(27))-en-1beta,2beta,3beta,4beta,5beta,7alpha,22xi,26-octaol-6-one-26-O-beta-D-glucopyranoside (1) and 5beta-furost-delta(25(27))-en-1beta,2beta,3beta,4beta,5beta,6beta,7alpha,22xi,26-nonaol-26-O-beta-D-glucopyranoside (2), on the basis of chemical and spectroscopic evidence. Both compounds displayed marked inhibitory action against NO production in rat abdomen macrophages induced by lipopolysaccharide (LPS) at 40 microg/mL.     

Withanolide derivatives from the roots of Withania somnifera and their neurite outgrowth activities

Five new withanolide derivatives (1, 9-12) were isolated from the roots of Withania somnifera together with fourteen known compounds (2-8, 13-19). On the basis of spectroscopic and physiochemical evidence, compounds 1 and 9-12 were determined to be (20S,22R)-3 alpha,6 alpha-epoxy-4 beta,5 beta,27-trihydroxy-1-oxowitha-24-enolide (1), 27-O-beta-D-glucopyranosylpubesenolide 3-O-beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranoside (withanoside VIII, 9), 27-O-beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranosylpubesenolide 3-O-beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranoside (withanoside IX, 10), 27-O-beta-D-glucopyranosylpubesenolide 3-O-beta-D-glucopyranoside (withanoside X, 11), and (20R,22R)-1 alpha,3 beta,20,27-tetrahydroxywitha-5,24-dienolide 3-O-beta-D-glucopyranoside (withanoside XI, 12). Of the isolated compounds, 1, withanolide A (2), (20S,22R)-4 beta,5 beta,6 alpha,27-tetrahydroxy-1-oxowitha-2,24-dienolide (6), withanoside IV (14), withanoside VI (15) and coagulin Q (16) showed significant neurite outgrowth activity at a concentration of 1 microM on a human neuroblastoma SH-SY5Y cell line.     

Design,Synthesis, and in vitro Antimicrobial Activity of New Furan/Thiophene‐1,3‐Benzothiazin‐4‐one Hybrids

This study presents the design, synthesis, spectral analysis, and in vitro antimicrobial evaluation of a new series of furan/thiophene‐1,3‐benzothiazin‐4‐one hybrids ( 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ). New compounds were obtained by cyclization reaction of N‐substituted furan/thiophene‐2‐carboxamide derivatives ( 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ) with thiosalicylic acid. All synthesized compounds were screened for their in vitro antimicrobial activities using the broth microdilution method. Nine of the synthesized compounds showed good activity against Gram‐positive, Gram‐negative bacteria, and yeasts belonging to Candida spp. (MIC = 7.81–500 μg/mL), especially against Staphylococcus spp. (MIC = 15.62–62.5 μg/ml), Bacillus spp. (MIC = 7.81–62.5 μg/mL), Bordetella bronchiseptica ATCC 4617 (MIC = 62.5–125 μg/mL), and fungistatic activity against Candida spp. (MIC = 62.5–125 μg/mL).     

Prenylated flavonoids with PTP1B inhibitory activity from the root bark of Erythrina mildbraedii

Phytochemical study on an EtOAc-soluble extract of the root bark of Erythrina mildbraedii resulted in the isolation of six prenylated flavonoids 1-6. Based on physicochemical and spectroscopic analyses, their structures were determined to be new natural products licoflavanone-4'-O-methyl ether (1), 2',7-dihydroxy-4'-methoxy-5'-(3-methylbut-2-enyl)isoflavone (2), and (3R)-2',7-dihydroxy-3'-(3-methylbut-2-enyl)-2',2'-dimethylpyrano[5',6' :4',5']isoflavan (3), along with three known compounds erythrinin B (4), abyssinin II (5), and parvisoflavone B (6). All the isolates, except for compound 4, inhibited PTP1B activity in vitro with IC(50) values ranging from 5.3 to 42.6 microM. This result further suggests that the prenyl group on the B ring of flavonoids plays an important role in suppressing the enzyme PTP1B.     

Chemical constituents of Melicope ptelefolia

Phytochemical investigations on the methanolic extract of Melicope ptelefolia Champ ex Benth. resulted in the isolation of three new compounds, identified as 3beta-stigmast-5-en-3-ol butyl tridecanedioate (melicoester) (1), (2Z, 6Z, 10Z, 14Z, 18Z, 22Z, 26E)-3', 7', 11', 15', 19', 23', 27', 31'-octamethyldotriaconta-2, 6, 10, 14, 18, 22, 26, 30-octadecanoate (melicopeprenoate) (2) and p-O-geranyl-7"-acetoxy coumaric acid (3). The compounds were isolated along with twenty-one other known compounds, lupeol (4), oleanolic acid (5), kokusaginine (6) genistein (7), p-O-geranyl coumaric acid (8), 4-stigmasten-3-one (9), 3beta-hydroxystigma-5-en-7-one (10) cis-phytyl palmitate (11), dodecane, dodecan-1-ol, ceryl alcohol, hentriacontanoic acid, eicosane, n-amyl alcohol, caprylic alcohol, octatriacontane, nonatriacontane, hexatriencontan-1-ol, methyl octacosanoate, beta-sitosterol, beta-sitosterol glucoside. Structures of all the compounds were established on the basis of MS and 1D and 2D NMR spectral data, as well as comparison with reported data.     

Synthesen und Thermolysen von 1-Alkinyl-2-methyl-1,2-epoxy-cycloalkanen. - Versuche zur Ringerweiterung um drei Kohlenstoffatome

Syntheses and Thermolyses of 1-Alkynyl-2-methyl-1,2-epoxy-cycloalkanes. - Attempts at Ring Enlargement by Three Carbon Atoms The 1-alkynyl-2-methyl-1,2-epoxy-alkene 2 and -cycloalkenes 9, 28 and 29 were obtained by epoxidation of the conjugated en-ynes 1, 7, 26 and 27 . The 12-membered ring en-ynes 26 and 27 were synthesized by ethynylation or propynylation of 2-methylcyclododecanone ( 19 ) to the 1-ethynyl- or 1-(1′-propynyl)-cyclododecanols 20 A/B and 21 A/B , respectively, followed by dehydration to give separable mixtures of the regio- and stereoisomeric en-ynes 22, 24, 26 and 23, 25, 27 , respectively. Gas-phase thermolyses of the epoxides 2, 9, 28 and 29 were carried out under reduced pressure through a quartz tube at 550–600°. The formation of 5-hexine-2-one ( 3 ) and 4,5-hexadien-2-one ( 4 ) from 2 can be explained by [1, 5]- and [1, 3]- hydrogen shifts, respectively, and subsequent Claisen-type rearrangements. Thermolysis of the six-membered carbocyclic epoxide 9 induced the expected ring expansion by three carbon atoms to give 14% 4-cyclononynone ( 12 ), along with the ketones 13, 14 and 15 as by-products, which probably arose from surface induced heterolytic C, O-bond fission and Wagner-Meerwein-type rearrangement processes. Preliminary experiments with the thermolysis of the 12-membered carbocyclic ethynyl-epoxide 28 , yielded a mixture, which contained 4-cyclopentadecynone ( 30 ) and afforded, after hydrogenation, cyclopentadecanone ( 31 , exaltone®) in 36% yield as the semicarbazone. Traces of 3-methylcyclopentadecanone ( 32 , rac, -muscone) were identified after thermolysis and hydrogenation of the propynyl-epoxide 29 .     

Structural requirements of flavonoids and related compounds for aldose reductase inhibitory activity

The methanolic extracts of several natural medicines and medicinal foodstuffs were found to show an inhibitory effect on rat lens aldose reductase. In most cases, flavonoids were isolated as the active constituents by bioassay-guided separation, and among them, quercitrin (IC(50)=0.15 microM), guaijaverin (0.18 microM), and desmanthin-1 (0.082 microM) exhibited potent inhibitory activity. Desmanthin-1 showed the most potent activity, which was equivalent to that of a commercial synthetic aldose reductase inhibitor, epalrestat (0.072 microM). In order to clarify the structural requirements of flavonoids for aldose reductase inhibitory activity, various flavonoids and related compounds were examined. The results suggested the following structural requirements of flavonoid: 1) the flavones and flavonols having the 7-hydroxyl and/or catechol moiety at the B ring (the 3',4'-dihydroxyl moiety) exhibit the strong activity; 2) the 5-hydroxyl moiety does not affect the activity; 3) the 3-hydroxyl and 7-O-glucosyl moieties reduce the activity; 4) the 2-3 double bond enhances the activity; 5) the flavones and flavonols having the catechol moiety at the B ring exhibit stronger activity than those having the pyrogallol moiety (the 3',4',5'-trihydroxyl moiety).     

Aminoacids in the synthesis of heterocyclic systems. The synthesis of methyl 2-acetylamino-3-dimethylaminopropenoate and 2-(N-methyl-N-trifluoroacetyl)amino-3-dimethylaminopropenoate and their application in the synthesis of heterocyclic compounds

Methyl (Z)-2-acetylamino-3-dimethylaminopropenoate (3) was prepared from N-acetylglycine (1), which was converted with N,N-dimethylformamide and phosphorus oxychloride into 4-dimethylaminomethylene-2-methyl-5(4H)-oxazolone (2), followed by treatment with methanol in the presence of potassium carbonate, into 3. The compound 3 was shown to be a versatile reagent in the synthesis of various heterocyclic systems. With N-nucleophiles, such as heterocyclic amines 4, either methyl 2-acetylamino-3-heteroarylaminopropenoates 5 or fused pyrimidinoncs 6 were formed, dependent on the reaction conditions and/or heterocyclic substituents: C-nuclcophiles with an active or potentially active methylene group, such as 1,3-dicarbonyl compounds 7, 8 and 9, substituted phenols 10a,b, naphthols 11, 12a-c, and substituted coumarin 13a, afforded substituted pyranones 20 and 22, and fused pyranones 21, 23–26. The nitrogen containing heterocycles 14–19 produced pyranoazines 27–31 and pyranoazole 32. In all of these systems the acetylamino group is attached at position 3 of the newly formed pyranone ring. The orientation around the double bond for methyl (Z)-2-(N-methyl-N-trifluo-roacetyl)-3-dimethylaminopropenoate (36) was established by X-ray analysis.     

Pteridines. Part LXXXVII. Synthesis and Properties of 8-Substituted 2-Thiolumazines

Various 8-substituted 2,8-dihydro-2-thioxopteridin-4(3H)-ones ( 14 – 21 ) and 2-(methylthio)pteridin-4(8H)-ones ( 27 – 32 ) have been synthesized by condensation of the appropriate 5-amino-6-(substituted amino)-1,2-dihydro-2-thioxopyrimidin-4(3H)-ones ( 22 – 34 ) and 5-amino-6-(substituted amino)-2-(methylthio)pyrimidin-4(3H)-ones ( 25 , 26 ), respectively, with glyoxal, biacetyl, and benzil. The presence of a quinonoid cross-conjugated π-electron system makes this type of compounds susceptible to nucleophilic additions in position 7, which leads to intramolecular ( 43 , 45 ) and intermolecular ( 44 ) covalent adducts. The newly synthesized compounds have been characterized by elemental analyses, pK_a determinations, ¹H-NMR and UV spectra. UV-Spectral changes in dependence of the pH are associated with the most appropriate molecular species including the monocations, neutral forms, covalent adducts, mono- and dianions.     

Synthesis,anti‐inflammatory,and anticancer activity evaluation of some heterocyclic amidine and bis‐amidine derivatives

Heterocyclic amidine derivatives of benzothiazole ( 6a , 6b , 6c ), benzimidazole ( 6d , 6e , 6f ), benzoxazole ( 6g , 6h , 6i ), and bis‐amidine derivatives of pyrimidine, ( 7a , 7b ) & triazole ( 7c , 7d , 7e ) ring system have been synthesized by nucleophilic addition reaction. All these compounds were screened for anti‐inflammatory and anticancer activities. At a dose of 50 mg/kg p.o., compounds 6c (39%), 6e (39%), and 6f (39%) exhibited anti‐inflammatory activity comparable to standard drug ibuprofen, which showed 39% activity and compounds 6b , 6e , 7a , and 7c exhibited moderate anticancer activity against cervix (HELA); neuroblastoma (IMR‐32); breast (MCF‐7), leukemia (THP‐1); and cervix (HELA) human cancer cell lines, respectively. J. Heterocyclic Chem., (2011).     

Synthesis and Biological Evaluation of New Dipyridylpteridines,Lumazines, and Related Analogues

Condensation of 4,5‐diaminopyrimidines 2 and 3 with 2,2ʹ‐dipyridil ( 4 ) afforded 6,7‐bis(2‐pyridyl)pteridine‐2‐one analogues 5 and 7 , respectively. Analogously, 6,7‐bis(2‐pyridyl)luamzine derivatives 13 , 15 , 17 , and 23 were synthesized from reaction of 5,6‐diamino‐2‐thiopyrimidines 13 , 14 , and 22 with 4 , respectively, while condensation of 4,5,6‐triaminopyrimidines ( 25 ) or 5,6‐diamino analogue 26 with 4 furnished the 4‐amino‐pteridine analogue 27 and 28 , respectively. Thiation of the new pteridines and lumazines afforded the 4‐thio analogues 6 , 8 , 16 , and 24 . Treatment of 6 and 8 with methanolic ammonia afforded the 4‐isopterine analogues 9 and 10 , respectively. Alkylation of 15 with substituted phenacyl chloride furnished 18 and 19 , which cyclized to the thiazolo‐pteridine derivatives 20 and 21 , respectively, on treatment with polyphosphoric acid. Alternatively, 27 was prepared from treatment of 24 with methanolic ammonia under drastic conditions. Condensation of 2 or 29 with 2‐oxo‐2‐(thiophen‐2‐yl)acetaldehyde oxime ( 11 ) gave the 6‐(2‐thienyl)‐pteridine‐4‐one ( 12 ) and 5‐chloro‐2‐(2‐thienyl)pyrido[3,4‐b ]pyrazine ( 31 ), respectively. All compounds were evaluated for their antiviral activity against the replication of HIV‐1 and HIV‐2 in MT‐4. Some of the synthesized compounds were tested against the bacterial species, Escherichia coli and Staphylococcus aureus , as well as fungal species, Candida tropicalis and Candida albicans .     

Antibacterial activity of the flavonoids from Dalbergia odorifera on Ralstonia solanacearum

Phytohemical investigation on the heartwood of Dalbergia odorifera resulted in the isolation of nine flavonoids. Their structures were elucidated as sativanone (1), (3R)-vestitone (2), (3R)-2',3',7-trihydroxy-4'-methoxyisoflavanone (3), (3R)-4'-methoxy-2',3,7-trihydroxyisoflavanone (4), carthamidin (5), liquiritigenin (6), isoliquiritigenin (7), (3R)-vestitol (8), and sulfuretin (9) based on their spectral data. All compounds were evaluated for their inhibitory activity against Ralstonia solanacearum. This is the first report about anti-R. solanacearum activity of the compounds from D. odorifera.     

Synthesis and Activity Evaluation of Novel Prenylated Flavonoids as Antiproliferative Agents

Twenty prenylated flavonoids 1-20 were synthesized by glycoside hydrolysis, dehydrogenation, selective O-methylation, O-prenylation and Claisen rearrangement reaction, from abundant and inexpensive natural flavonoids naringin, hespiredin, quercetin and myricetin. Among them, 1-7, 10-15 and 17-20 are novel compounds, the natural product 3,3',4',7-tetramethoxy-8-prenyl-5-hydroxy flavonoid(16) was synthesized in a high yield. Their antiprolirative activities were evaluated in vitro on a panel of three human cancer cell lines(HeLa, HCC1954 and SK-OV-3). The results show that most of the target compounds displayed moderate to potent antiprolirative activities against the three cancer cells with half maximal inhibitory concentration(IC₅₀) values from 0.49 μmol/L to 95.07 μmol/L. Among them, 3',4',7-trimethoxyl-5-hydroxyl-8-prenyl flavonoid(12) exhibited the strongest antiprolirative activity against the three cancer cells mentioned above with IC₅₀ values of 0.91-7.08 μmol/L. 3',7-Dimethoxy-5-O-prenyl flavone(6) and 3',4',7-trimethoxy-5-O-prenyl flavone(10) showed selective antiproliferative activity against HCC1954 cells with IC₅₀ value of 0.49 and 5.32 μmol/L, respectively.     

Antioxidant and Anti-Inflammatory Activities of Six Flavonoids from Smilax glabra Roxb

This study aimed to isolate, prepare and identify the main flavonoids from a standardized Smilax glabra flavonoids extract (SGF) using preparative HPLC, MS, ¹H NMR and ¹³C NMR, determine the contents of these flavonoids using UPLC, then compare their pharmacological activities in vitro. We obtained six flavonoids from SGF: astilbin (18.10%), neoastilbin (11.04%), isoastilbin (5.03%), neoisoastilbin (4.09%), engeletin (2.58%) and (−)-epicatechin (1.77%). The antioxidant activity of six flavonoids were evaluated by determining the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and 2,2′-Azinobis (3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt (ABTS⁺) radical scavenging activity and ferric reducing antioxidant power (FRAP). In addition, the anti-inflammatory activity of six flavonoids were evaluated by determining the production of cytokines (IL-1β, IL-6), nitric oxide (NO) using enzyme linked immunosorbent assay and the NF-κB p65 expression using Western blotting in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The results showed that (−)-epicatechin, astilbin, neoastilbin, isoastilbin and neoisoastilbin had strong antioxidant activities, not only in DPPH and ABTS⁺ radicals scavenging capacities, but in FRAP system. Furthermore, all the six flavonoids could significantly inhibit the secretion of IL-1β, IL-6, NO (p < 0.01) and the protein expression of NF-κB p-p65 (p < 0.01) in LPS-stimulated RAW264.7 cells. This study preliminarily verified the antioxidant and anti-inflammatory activities of six flavonoids in S. glabra.