A new indole glycoside from the seeds of <Emphasis Type="Italic">Raphanus sativus</Emphasis>

A new indole glycoside, β-d-glucopyranosyl 2-(methylthio)-1H-indole-3-carboxylate, named raphanuside A (1), as well as eight known compounds, β-d-fructofuranosyl-(2 → 1)-(6-O-sinapoyl)-α-d-glucopyranoside (2), (3-O-sinapoyl)-β-d-fructofuranosyl-(2 → 1)-α-d-glucopyranoside (3), (3-O-sinapoyl)-β-d-fructofuranosyl-(2 → 1)-(6-O-sinapoyl)-α-d-glucopyranoside (4), (3,4-O-disinapoyl)-β-d-fructofuranosyl-(2 → 1)-(6-O-sinapoyl)-α-d-glucopyranoside (5), isorhamnetin 3,4′-di-O-β-d-glucoside (6), isorhamnetin 3-O-β-d-glucoside-7-O-α-l-rhamnoside (7), isorhamnetin 3-O-β-d-glucoside (8) and 3'-O-methyl-(?)-epicatechin 7-O-β-d-glucoside (9) were isolated from the seeds of Raphanus sativus. Furthermore, compounds 1–3 and 6–9, were isolated from this plant for the first time. The structures of compounds 1–9 were identified using 1D and 2D NMR, including ¹H–¹H COSY, HSQC, HMBC and NOESY spectroscopic analyses. The inhibitory activity of these isolated compounds against interleukin-6 (IL-6) production in TNF-α stimulated MG-63 cells was also examined.     

Two new naphthalenic lactone glycosides from <Emphasis Type="Italic">Cassia obtusifolia</Emphasis> L. seeds

Two new naphthalenic lactone glycosides, (3S)-9,10-dihydroxy-7-methoxy-3-methyl-1-oxo-3,4-dihydro-1H-benzo[g]isochromene-3-carboxylic acid 9-O-β-d-glucopyranoside (1) and (3R)-cassialactone 9-O-β-d-glucopyranoside (2) were isolated from seeds of Cassia obtusifolia Linn., along with five known compounds: (3R)-cassialactone 9-O-β-d-gentiobioside (3), emodin 1-O-β-gentiobioside (4), 1-hydroxyl-2-acetyl-3,8-dimethoxy-naphthalene 6-O-β-d-apiofuranosyl-(1?→?2)-β-d-glucopyranoside (5), rubrofusarin 6-O-β-d-gentiobioside (6), rubrofusarin 6-O-β-d-triglucoside (7). Structures of 1 and 2 were elucidated by NMR and HR-ESI-MS spectroscopic analysis. Their stereochemistry was determined by CD experiment. All compounds were tested for their ability to inhibit the formation of advanced glycation end-products in vitro. Compounds 1, 2, 3, 5, and 6 showed significant in vitro inhibitory activities (IC₅₀ values of 11.63, 23.40, 7.32, 89.03, and 38.89 µM, respectively).     

Two new ursane-type triterpenoid saponins from <Emphasis Type="Italic">Elsholtzia bodinieri</Emphasis>

Two new ursane-type triterpenoid saponins, bodiniosides M (1) and N (2), along with three known saponins, oblonganosides I (3), pseudobuxussaponin B (4) and bodinioside A (5), were isolated from the aerial parts of Elsholtzia bodinieri. The structures of compounds 1 and 2 were characterized by spectroscopic data as well as acid hydrolysis and GC analysis as 3-O-β-d-xylopyranosyl-19α-hydroxy-23-acetoxy-urs-12(13)-en-28-oic acid 28-O-α-l-rhamnopyranosyl-(1-2)-β-d-glucopyranoside and 3-O-β-d-glucopyranosyl-2α,19α-dihydroxy-urs-12(13)-en-28,20β-lactone. Compounds 1 and 5 exhibited potent anti-HCV activities in vitro with a selective index of 6.53 and 4.41, respectively.     

Antimicrobial glycoalkaloids from the tubers of <Emphasis Type="Italic">Stephania succifera</Emphasis>

Three new glycoalkaloids, N-formyl-asimilobine-2-O-β-d-glucoside (1), (?)-1-O-β-d-glucoside-8-oxotetrahydropalmatine (2), and 1-N-monomethylcarbamate-argentinine-3-O-β-d-glucoside (3) were isolated from tubers of Stephania succifera. The structures were established based on spectroscopic analysis, and the antimicrobial activities of the three glycoalkaloids are reported.     

Antioxidant <Emphasis Type="Italic">C</Emphasis>-glycosylflavones of <Emphasis Type="Italic">Drymaria cordata</Emphasis> (Linn.) Willd

A new C-glycosylflavone, drymaritin E (6-C-(3-keto-β-digitoxopyranosyl)-4′-O-(β-d-glucopyranosyl)-7-methoxyl-5,4′-dihydroxylflavone) 1 was isolated from the oily upper phase (SU) of the MeOH extract from aerial parts of Drymaria cordata together with two known compounds (cassiaoccidentalin A 2 and anemonin 3) and an inseparable mixture of two known C-glycosylflavones 5,4′-dihydroxy-7-methoxyflavone-6-C-(2′′-O-α-l-rhamnopyranosyl)-β-d-glucopyranoside 4a and 5,7,3′,4′-tetrahydroxyflavone-6-C-(2′′-O-α-l-rhamnopyranosyl)-β-d-glucopyranoside 4b. The alkaline hydrolysis of 3 led to a new hemisynthetic derivative, sodium anemonate (sodium 2-((1’E) 2′-sodium-carboxylate-vinyl)-5-oxo-cyclohex-1-ene carboxylate) 3a. The chemical structures were determined by spectroscopic methods (¹H NMR, ¹³C NMR, ¹H-¹H COSY, HMBC, HSQC, and NOESY) and mass spectrometry (ESI–MS). C-glycosylflavones had significant free radical-scavenging activities on the radical 2,2-diphenyl-1-picrylhydrazyl (DPPH). However, SU and compounds 3 and 3a exhibited no activity. In particular, compound 1 exhibited a concentration-dependent radical scavenging activity on DPPH with EC₅₀ of 31.43 µg/mL.     

Phenylacylphenol derivatives with anti-melanogenic activity from <Emphasis Type="Italic">Stewartia pseudocamellia</Emphasis>

Three new phenylacylphenol derivatives, stewartianol (1), deoxystewartianol-4′-O-arabinoglucoside (2), and stewartianol-3-O-glucoside (3), along with nine known compounds, methylesculin (4), fraxoside (5), fraxetin (6), scopletin (7), (+)-dihydromyricetin (8), (+)-taxifolin-7-O-β-d-glucose (9), (+)-taxifolin (10), (+)-dihydrokaempferol-7-O-β-d-glucose (11), and 3-acetyl-ursolic acid (12), were isolated from the twigs of Stewartia pseudocamellia; commonly used as folk medicine in Korea. The structures of the isolated compounds were identified using spectroscopic analysis, including 1D, 2D NMR, MS and compared with published data. The compounds were tested for their anti-melanogenic activity in cultured murine B16 melanoma cells. Stewartianol (1) and stewartianol-3-O-glucoside (3) showed an inhibitory effect significantly on melanogenesis in a concentration-dependent manner.     

New podolactones from the seeds of <Emphasis Type="Italic">Podocarpus nagi</Emphasis> and their anti-inflammatory effect

Podolactones are a class of structural diverse diterpenoid lactones, mainly isolated from the Podocarpus species. Several bioactivities have been disclosed for podolactones, including cytotoxicity and anti-atherosclerosis. In this study, the seeds of P. nagi were isolated by comprehensive chromatographic methods to obtain three new podolatones, named nagilactone B 1-O-β-d-glucoside (1), nagilactone N3 3-O-β-d-glucoside (2), and 2-epinagilactone B (3), as well as a known compound, nagilactone B (4). Their structures were determined by analyses of NMR and HRESIMS data. Compounds 1 and 2 significantly inhibited nitric oxide (NO) production on LPS-stimulated RAW264.7 macrophages, with IC₅₀ values of 0.18?±?0.04 and 0.53?±?0.03 μM, respectively. Indomethacin (IC₅₀ 4.21?±?0.32 μM) was used as a positive control. Compound 1 suppressed the expression of inducible NO synthase (iNOS) in a concentration-dependent manner, mediating through inhibiting nuclear factor-κB (NF-κB) activity. This is the first report regarding the anti-inflammatory effect of podolactones, which could be potential anti-inflammatory agents.     

Simultaneous analysis of seven marker compounds from Saposhnikoviae Radix,Glehniae Radix and Peucedani Japonici Radix by HPLC/PDA

A new combination of high performance liquid chromatography (HPLC) method coupled with photodiode array (PDA) analysis has been developed for the simultaneous quantitative determination of seven major components in Saposhnikoviae Radix (SR), Glehniae Radix (GR) and Peucedani Japonici Radix (PR), namely peucedanol 7-O-β-d-glucopyranoside (1), prim-O-glucosylcimifugin (2), cimifugin (3), 4′-O-β-d-glucosyl-5-O-methylvisamminol (4), bergapten (5), sec-O-glucosylhamaudol (6), and imperatorin (7). Clear separation of these seven components were achieved on a Phenomenex Kinetex C18 (250 × 4.6 mm, 5 μm) column by gradient elution of water (A) and methanol (B) as mobile phase. The flow rate was 1.0 mL/min and the UV detector wavelength was set at 254 nm. The method was successfully used in the analysis of SR, GR, and PR with relatively simple conditions and procedures, and the results were satisfactory for linearity, recovery, precision, accuracy, stability and robustness. The results indicate that the established HPLC/PDA method is suitable for the classification of SR, GR, and PR.     

Synthesis of novel <Emphasis Type="Italic">N</Emphasis>-acyl-<Emphasis Type="Italic">β</Emphasis>-<Emphasis Type="SmallCaps">d</Emphasis>-glucopyranosylamines and ureas as potential lead cytostatic agents

Novel classes of acetylated and fully deprotected N-acyl-β-d-glucopyranosylamines and ureas have been synthesized and biologically evaluated. Acylation of the per-O-acetylated β-d-glucopyranosylurea (5), easily prepared via its corresponding phosphinimine derivative, by zinc chloride catalyzed reaction of the corresponding acyl chlorides RCOCl (a–f) gave the protected N-acyl-β-d-glucopyranosylureas (6a–f), in acceptable-to-moderate yields. Subsequent deacetylation of analogues 6a–f under Zemplén conditions afforded the fully deprotected derivatives 7a,b,d,e,f, while the desired urea 7c was formed after treatment of 6c with dibutyltin oxide. All protected and unprotected compounds were examined for their cytotoxic activity in different L1210, CEM and HeLa tumor cell lines and were also evaluated against a broad panel of DΝΑ and RNA viruses. Derivative 7c exhibited cytostatic activity against the three evaluated tumor cell lines (IC₅₀ 9–24 μΜ) and might be the basis for the synthesis of structure-related derivatives with improved cytostatic potential. Only analogue 6f weakly but significantly inhibited the replication of parainfluenza-3 virus, Sindbis virus and Coxsackie virus B4 in cell cultures at concentrations of 45–58 μM.     

New ursane triterpenoids from <Emphasis Type="Italic">Ficus pandurata</Emphasis> and their binding affinity for human cannabinoid and opioid receptors

Phytochemical investigation of Ficus pandurata Hance (Moraceae) fruits has led to the isolation of two new triterpenoids, ficupanduratin A [1β-hydroxy-3β-acetoxy-11α-methoxy-urs-12-ene] (11) and ficupanduratin B [21α-hydroxy-3β-acetoxy-11α-methoxy-urs-12-ene] (17), along with 20 known compounds: α-amyrin acetate (1), α-amyrin (2), 3β-acetoxy-20-taraxasten-22-one (3), 3β-acetoxy-11α-methoxy-olean-12-ene (4), 3β-acetoxy-11α-methoxy-12-ursene (5), 11-oxo-α-amyrin acetate (6), 11-oxo-β-amyrin acetate (7), palmitic acid (8), stigmast-4,22-diene-3,6-dione (9), stigmast-4-ene-3,6-dione (10), stigmasterol (12), β-sitosterol (13), stigmast-22-ene-3,6-dione (14), stigmastane-3,6-dione (15), 3β,21β-dihydroxy-11α-methoxy-olean-12-ene (16), 3β-hydroxy-11α-methoxyurs-12-ene (18), 6-hydroxystigmast-4,22-diene-3-one (19), 6-hydroxystigmast-4-ene-3-one (20), 11α,21α-dihydroxy-3β-acetoxy-urs-12-ene (21), and β-sitosterol-3-O-β-d-glucopyranoside (22). Compound 21 is reported for the first time from a natural source. The structures of the 20 compounds were elucidated on the basis of IR, 1D (¹H and ¹³C), 2D (¹H–¹H COSY, HSQC, HMBC and NOESY) NMR and MS spectroscopic data, in addition to comparison with literature data. The isolated compounds were evaluated for their anti-microbial, anti-malarial, anti-leishmanial, and cytotoxic activities. In addition, their radioligand displacement affinity on opioid and cannabinoid receptors was assessed. Compounds 4, 11, and 15 exhibited good affinity towards the CB2 receptor, with displacement values of 69.7, 62.5 and 86.5 %, respectively. Furthermore, the binding mode of the active compounds in the active site of the CB2 cannabinoid receptors was investigated through molecular modelling.     

Chemical structures of constituents from the leaves of <Emphasis Type="Italic">Polyscias balfouriana</Emphasis>

A new pyrrolidine derivative, (5S)-hydroxyethyl 2-oxopyrrolidine-5-carboxylate (1), a new flavonol glycoside, tamaraxetin 3,7-di-O-α-l-rhamnopyranoside (2), and a new triterpene saponin, polyscioside A methyl ester (3), along with six known compounds (4–9) were isolated from the leaves of Polyscias balfouriana. Their chemical structures were elucidated on the basis of extensive spectroscopic analysis.     

Alkyl phenols,alkenyl cyclohexenones and other phytochemical constituents from <Emphasis Type="Italic">Lannea rivae</Emphasis> (chiov) Sacleux (Anacardiaceae) and their bioactivity

Six novel compounds, 3-nonadec-14′-(Z)-enyl phenol (1a); 4,5-dihydroxy-4,2′-epoxy-5-[16′-Z-18′-E-heneicosenyldiene]-cyclohex-2-enone (2), 2,4,5-trihydroxy-2-[16′-Z-heneicosenyl]-cyclohexanone (3); 4S,6R-dihydroxy-6-[12′-Z-heptadecenyl]-cyclohex-2-enone (4a); 4S,6R-dihydroxy-6-[14′-Z-nonadecenyl]-cyclohex-2-enone (4b); and 1,2,4-trihydroxy-4-[16′-Z-heneicosenyl]-cyclohexane (5) were identified from the roots and stems of Lannea rivae in addition to the known cardanols, 3-heptadec-12′-Z-enyl phenol (1b), 3-pentadec-10′-Z-enyl phenol (1c) and 3-pentadecyl phenol (1d), sitosterol (6), sitosterol glucoside (7), taraxerone (8), taraxerol (9), E-lutein (10), myricetin (11), myricetin-3-O-α-rhamnopyranoside (12), myricetin-3-O-β-galactopyranoside (13) and (-)-epicatechin-3-O-gallate (14). The ketones 4a and 4b were isolated as a mixture and were qualitatively separated and identified by GCMS. Myricetin (11) and epicatechin gallate (14) displayed over 90 % DPPH radical-scavenging activity at 50 μg mL^?1, while its glycosides (12 and 13) showed percentages of over 70 % in the same assay. The same compounds 11 and 14 showed antibacterial activity similar to erythromycin and vancomycin against Gram-positive bacteria and were also active against Gram-negative bacteria, but not as much as the cefuroxime, ciprofloxacin and nalidixic acid standards. Compounds 1a–d, 4a–b and 5 were all relatively non-toxic, while 2 (the epoxy cyclohex-2-enone) and 3 (the trihydroxy cyclohexanone) showed more toxicity than the others. These two toxic compounds, 2 and 3 also showed antiplasmodial activity with IC₅₀ values between 0.48 and 2.05 μg mL^?1. The mixture of dihydroxy cyclohex-2-enones 4a and 4b, which was far less toxic than 2 and 3, also showed promising antiplasmodial activity and may be a possible lead for further investigation as an antiplasmodial drug.     

C<Subscript>21</Subscript> steroid derivatives from the Dai herbal medicine Dai-Bai-Jie,the dried roots of <Emphasis Type="Italic">Marsdenia tenacissima</Emphasis>, and their screening for anti-HIV activity

Twenty-three new C₂₁ steroidal glycosides, marstenacissides C1–C10 (1–10), D1–D7 (11–17) and E1–E6 (18–23), and four new C₂₁ steroids, 11α,12β-O-ditigloyl-tenacigenin C (24), 11α-O-benzoyl-12β-O-tigloyl-tenacigenin C (25), 11α-O-tigloyl-12β-O-benzoyl-tenacigenin C (26) and 11α-O-tigloyl-12β-O-benzoyl-marsdenin (27), were isolated from the Dai herbal medicine Dai-Bai-Jie, derived from the roots of Marsdenia tenacissima. The chemical structures of all compounds were established by spectroscopic techniques, including high-resolution mass spectrometry and NMR spectroscopy, as well as by comparison with reported spectral data. The anti-HIV activities of these compounds were screened, and the compounds obtained displayed inhibitory effects against HIV-1 with inhibition rates of 36.4–81.3% at 30 μM.     

Degranulation inhibitors from the arils of <Emphasis Type="Italic">Myristica fragrans</Emphasis> in antigen-stimulated rat basophilic leukemia cells

A methanol extract of mace, the aril of Myristica fragrans (Myristicaceae), was found to inhibit the release of β-hexosaminidase, a marker of antigen-IgE-stimulated degranulation in rat basophilic leukemia cells (RBL-2H3, IC₅₀ = 45.7 μg/ml). From the extract, three new 8-O-4′ type neolignans, maceneolignans I–K (1–3), were isolated, and the stereostructures of 1–3 were elucidated based on spectroscopic and chemical evidence. Among the isolates, maceneolignans A (5), D (6), and H (8), (?)-(8R)-?^8′-4-hydroxy-3,3′,5′-trimethoxy-8-O-4′-neolignan (13), (?)-(8R)-?^8′-3,4,5,3′,5′-pentamethoxy-8-O-4′-neolignan (14), (?)-erythro-(7R,8S)-?^8′-7-acetoxy-3,4-methylenedioxy-3′,5′-dimethoxy-8-O-4′-neolignan (17), (+)-licarin A (20), nectandrin B (24), verrucosin (25), and malabaricone C (29) were investigated as possible degranulation inhibitors (IC₅₀ = 20.7–63.7 μM). These inhibitory activities were more potent than those of the antiallergic agents tranilast (282 μM) and ketotifen fumalate (158 μM). Compounds 5, 25, and 29 also inhibited antigen-stimulated tumor necrosis factor-α production (IC₅₀ = 39.5–51.2 μM), an important process in the late phase of type I allergic reactions.     

A new cyclic dipeptide penicimutide: the activated production of cyclic dipeptides by introduction of neomycin-resistance in the marine-derived fungus <Emphasis Type="Italic">Penicillium</Emphasis><Emphasis Type="Italic">purpurogenum</Emphasis> G59

A novel cyclic dipeptide, named penicimutide (1), and four known cyclic dipeptides, cyclo(l-Val-l-Pro) (2), cyclo(l-Ile-l-Pro) (3), cyclo(l-Leu-l-Pro) (4) and cyclo(l-Phe-l-Pro) (5), were isolated from a neomycin-resistant mutant of the marine-derived fungus Penicillium purpurogenum G59. The structure of 1, including the absolute configuration, was determined by spectroscopic and chemical methods, especially NMR and Marfey’s analysis. An unusual amino acid in 1, 4,5-didehydro-l-leucine, was found for the first time occurring in nature. HPLC–ESI–MS analysis evidenced that 1–3 were produced only in the mutant strain, but 4 and 5 were produced in both the mutant and parental strains, indicating that the introduction of neomycin-resistance in the mutant activated pathways of 1–3 biosynthesis that were silent in the parental strain. Compound 1 selectively inhibited HeLa cells (among five tested human cancer cell lines) with an inhibition rate (IR %) of 39.4 % at 100 µg/mL, a similar inhibition intensity to that of the positive control 5-fluorouracil (IR % of 41.4 % at 100 µg/mL against HeLa cells). The present work exemplifies the effectiveness of our previous DMSO-mediated method for introducing drug-resistance in fungi to activate silent biosynthetic pathways to obtain new bioactive compounds.     

Bioactive flavanoids from <Emphasis Type="Italic">Glycosmis arborea</Emphasis>

Background

Glycosmis is a genus of evergreen glabrous shrub and distributed all over India. It possesses various medicinal properties and is used in indigenous medicine for cough, rheumatism, anemia, and jaundice. Glycosmis arborea is a rich source of alkaloids, terpenoids, coumarins, as well as flavonoids.

Results

The chemical investigation of methanol fraction of the leaves of G. arborea led to the isolation of one new flavone C-glycoside along with three known flavanoids, named as 5,7-dihydroxy-2-[4-hydroxy-3-(methoxy methyl) phenyl]-6-C-β-d-glucopyranosyl flavone (4), 5,7,4^′-trihydroxy-3^′-methoxy flavone (1), 5,4^′-dihydroxy-3^′-methoxy-7-O-β-d-glucupyranosyl flavanone (2), and 5,4^′-dihydroxy-3^′-methoxy-7-O-(α-l-rhamnosyl-(1?→6?)-β-d-glucopyranosyl) flavanone (3), respectively. The structures of all compounds were elucidated with the help of nuclear magnetic resonance spectrometry. Pure compounds and fractions were evaluated for pest antifeedant and antimicrobial activity.

Conclusion

Four compounds were isolated from the leaves of G. arborea. Among them, compound 4 showed significant antimicrobial activity.

     

Microbial transformation of naringenin derivatives

Microbial transformations of (±)-7-O-prenylnaringenin (7-PN, 1) and (±)-7-O-allylnaringenin (7-AN, 2) have isolated four metabolites (3–6). Structures of these novel compounds were identified as 5,4′-dihydroxy-7-O-[(2E)-4-hydroxy-3-methyl-2-buten-1-yl]flavanone (3), 5,4′-dihydroxy-7-O-(2,3-dihdroxy-3-methylbutyl)flavanone (4), 5,4′-dihydroxy-7-O-(2,3-dihdroxypropyl)flavanone (5), and 5-O-β-D-glucopyranosyl-7-O-allyl-4′-hydroxyflavanone (6) based on spectroscopy. Compounds 1–6 were evaluated for their radical scavenging capacity using DPPH (2,2-diphenyl-1-picrylhydrazyl). The derivatives 3–6 exhibited more potent antioxidant activity than their corresponding substrates 1 and 2.     

(−)-Catechin glycosides from Ulmus davidiana

Extensive chromatographic separation of the n-BuOH soluble fraction obtained from the stem and root barks of U. davidiana resulted in five hitherto unknown compounds together with a known one (?)-catechin 1. Structures of the five compounds were elucidated by chemical and spectroscopic analyses, to be (?)-catechin-7-O-gallate-5-O-(5″″-trans-caffeoyl)-β-d-apiofuranoside-3-O-β-d-apiofuranosyl-(1 → 2)-β-d-glucopyranoside 2, (?)-catechin-7-O-gallate-5-O-(5″″-trans-caffeoyl)-β-d-apiofuranoside-3-O-β-d-glucopyranoside 3, (?)-catechin-7-O-gallate-5-O-β-d-apiofuranoside-3-O-(2″-O-galloyl)-β-d-glucopyranoside 4, (?)-catechin-7-O-gallate-5-O-(5″″-trans-caffeoyl)-β-d-apiofuranoside 5, and (?)-catechin-7-O-gallate-5-O-(5″″-trans-feruloyl)-β-d-apiofuranoside 6.     

Synthesis and biological evaluation of novel <Emphasis Type="SmallCaps">d</Emphasis>-glucose-derived 1,2,3-triazoles as potential antibacterial and antifungal agents

A series of novel d-glucose-derived 1,2,3-triazoles have been synthesized in excellent yields via Cu(I)-catalyzed 1,3-dipolar cycloaddition by using methyl α-d-glucopyranoside as starting material. All the new compounds were confirmed by ¹H NMR, ¹³C NMR, IR, MS, and HRMS spectra, and their antimicrobial activities were screened against Gram-Positive, Gram-Negative bacteria, and fungi. Bioactive assay manifested that some of the synthesized glucose-derived 1,2,3-triazoles exhibited good antibacterial and antifungal activities. Notably, compound 5k gave the most potent efficiency with MIC₅₀ value of 6 µM against Candida albicans, which was nine-fold more active than the reference drug Fluconazole. It also exhibited good antibacterial activity against Escherichia coli with the MIC₅₀ value of 10.8 µM compared to Chloramphenicol while the corresponding hydrochloride 4k revealed remarkable inhibitory against Bacillus subtilis with an MIC₅₀ value of 11 µM.     

Synthesis of phenylazonaphtol-β-<Emphasis Type="SmallCaps">D</Emphasis>-<Emphasis Type="Italic">O</Emphasis>-glycosides,evaluation as substrates for beta-glycosidase activity and molecular studies

Background

Phenylazonaphtol-β-D-O-glycosides are alternative substrates for the detection of enzymatic activity of β-glycosidases which are involved in various important processes. These azoic compounds are currently exploited as prodrugs for colonic disease due the presence of β-glycosidase activity in the gut flora and therefore allowing the release of the drug at the specific site.

Results

Phenylazonaphtol-β-D-O-glucoside 3a and galactoside 3b were prepared via diazonium salt conditions under weak acidic conditions which do not compromise the O-glycosidic bond stability, by coupling reaction between 2-naphtol sodium salt with aminoglycosides 1a and 1b. The resulting phenylazonaphtol glycosides 2a and 2b were deprotected affording the phenylazonaphtol glycosides 3a and 3b in quantitative yield. The galactoside glycoside 3b was assayed as substrate for in vitro β-galactosidase enzymatic activity showing strong absorbance after releasing of the azoic chromophore. Also, docking studies were performed to determine the best pose as well as the interactions between the ligand and the residues located at the active site.

Conclusions

The methodology developed for synthesizing the phenylazonaphtol glycosides described proved to be convenient for generating azoic functionalities in the presence of glycosidic bonds and the glycosides suitable as alternative substrates and potentially useful prodrugs in the treatment of colonic diseases.

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