Inhibitors of α-glucosidase, α-amylase and lipase from Chrysanthemum morifolium

A new endoperoxysesquiterpene lactone, 10α-hydroxy-1α,4α-endoperoxy-guaia-2-en-12,6α-olide (1), together with a flavanone, eriodictyol (2), and two flavone glycosides, acacetin-7-O-β-d-glucopyranoside (3) and acacetin-7-O-α-l-rhamopyranoside (4), were isolated from the methanol extract of Chrysanthemum morifolium flowers by a bioassay-guided fractionation. Compound 1 showed strong inhibitory effects against α-glucosidase and lipase activities, with IC₅₀ values of 229.3 and 161.0 μM, respectively. The flavone glycosides 3 and 4 inhibited both α-glucosidase and α-amylase, while flavanone 2 was only effective against α-amylase.     

Enantioselective total synthesis,divergent optimization and preliminary biological evaluation of (indole-N-alkyl)-diketopiperazines

The first enantioselective total synthesis of the antifungal natural product (indole-N-isoprenyl)-tryptophan-valine diketopiperazine 5 was accomplished. Four stereoisomers of 5 were intentionally prepared, and the (R, R)-isomer is more favorable in enhancing the antifungal bioactivity. Divergent structural optimization of this attractive model was conducted from the chiral pool amino acids. Fine-tuning of the structure protruded the broad-spectrum antifungal 6b, which also showed good preventative efficacy against Sclerotinia scleotiorum. Compound 5d could accelerate both hypocotyl elongation and root growth of Eclipta prostrata even at the concentration of <2.5 ppm. This unique and easily accessible scaffold will be of prime importance in achieving agrochemical candidates with the novel scaffold.     

Chemical analysis of flavonoid constituents of the seagrass Halophila stipulacea: First finding of malonylated derivatives in marine phanerogams

The flavonoid fraction from the butanol extract of a Mediterranean sample of the seagrass Halophila stipulacea was chemically analyzed. A new malonylated flavone glucoside, genkwanin-4′-O-(6“-malonyl-glucopyranoside) (3), was isolated together with known flavone glucosides 4-9, previously reported only from terrestrial sources. The structure of 3 was established by means of spectroscopic techniques, mainly NMR methods.     

Isoflavonoids,flavonoids and flavans from Potentilla astracanica

Phytochemical investigation of the aerial parts of Potentilla astracanica Jacq. led to the isolation of two isoflavonoid glucosides (1, 2) five flavonoid glycosides (3–7) including one flavone-C-glycoside (7) as well as two flavans (8, 9). The occurrence of isoflavonoids and C-glycosyl flavone is being reported for the first time from the genus Potentilla.     

A lipase inhibitor monoterpene and monoterpene glycosides from Monarda punctata

An 80% acetone extract of Monarda punctata showed an inhibitory effect on lipase activity in isolated mouse plasma in vitro and carvacrol was obtained as the active constituent. It had an IC₅₀ value of 4.07 mM in vitro and suppressed elevations in blood triacylglycerol levels in olive oil-loaded mice. Furthermore, from the whole plant, 22 compounds were isolated. Six monoterpene glycosides (3–8), a flavone glucuronide (9), and other known compounds were identified based on the results of spectroscopic analyses.     

O-Prenylated flavonoids from Dalbergia sissoo

A chalcone, 2,3-dimethoxy-4′-γ,γ-dimethylallyloxy-2′-hydroxychalcone (1) and an isoflavone, 7-γ,γ-dimethylallyloxy-5-hydroxy-4′-methoxyisoflavone (2) together with a known flavone, 7-hydroxy-6-methoxyflavone (3), a known isoflavone, biochanin A (4) and a known rotenoid, dehydroamorphigenin (5) were isolated from the root bark of Dalbergia sissoo. The structures of compounds 1–5 were elucidated on the basis of spectral and chemical studies.     

Chrysoeriol derivatives and other constituents from Glandularia selloi

Glandularia selloi (Verbenaceae) presents phenylethanoids, iridoids and flavone glycosides as the main constituents. Two novel chrysoeriol derivatives, selloiside A (1) and selloiside B (2) were isolated from the methanolic extract of the aerial parts. Both flavones are acylated disaccharides. Two known compounds, verbascoside (3) and 6β-hydroxy-ipolamiide (4), were isolated from the methanolic extract of the roots. The structures were elucidated using 1D, 2D NMR and MS. Acylflavones have taxonomic significance since they occur mainly is species from the order Lamiales, specifically from the family Lamiaceae, closely related to Verbenaceae. The compounds 1 – 4 and the methanolic extract were investigated for antichemotactic activity.     

New sesterterpenoids and other constituents from Salvia dominica growing wild in Jordan

A new nor-oleanane triterpene 24-nor-4(23)-12-oleanadien-2α,3α,28-triol (1) and two new sesterterpenes salvidominicolide A (2), salvidominicolide B (3) together with fifteen known compounds were isolated from Salvia dominica L. growing wild in Jordan. The known compounds comprised six flavones, three triterpenes, one diterpene, one sesterterpene, two oxygenated monoterpenes, one sterol glucoside and one flavone glucoside. The isolated compounds were elucidated by extensive spectroscopic methods including NMR (1D and 2D), UV, IR and MS (HRMS).     

New C-2 diastereomers of flavanone glycosides conjugated with 3-hydroxy-3-methylglutaric acid from the pericarp of Citrus grandis (L.) Osbeck

Two new 3-hydroxy-3-methylglutaryl (HMG) flavanone 7-O-diglycosides, cigranosides A and B (1 and 2), the known naringenin 7-(2′′-α-rhamnosyl-6′′-(3′′′′-hydroxy-3′′′′-methylglutaryl)-glucoside (melitidin, 3), their common biosynthetic precursor flavanone 7-O-diglycoside (naringin, 4), and one known flavone 7-O-diglycoside (rhoifolin, 5) were isolated from the pericarp of Citrus grandis (L.) Osbeck. The structures of these compounds were elucidated by spectroscopic and chemical techniques. The relative ratios and absolute configurations of the C-2 diastereomers of compounds 1, 2 and 4 were determined by online normal-phase HPLC-CD using a Chiralcel column. The absolute configuration of the HMG fragment in compounds 1–3 was assigned to be S through spectroscopic analysis of the mevalonamide obtained by amidation and reduction of the HMG moiety. The NO inhibitory activities of compounds 1–5 were evaluated using lipopolysaccharide-induced RAW264.7 cells. Compounds 1–5 were not cytotoxic to RAW264.7 cells at 10 μM.     

Triterpenoid saponins from Piptadeniastrum africanum (Hook. f.) Brenan

One new triterpenoid saponin, named piptadeniaoside (1), along with two known saponins (2–3) have been isolated from the stem bark of Piptadeniastrum africanum. After previous isolation of flavone derivatives from this plant, new phytochemical investigations were performed for its saponin content. Their structures were established by direct interpretation of their spectral data, mainly HRESIMS, 1D NMR (¹H, ¹³C NMR, DEPT) and 2D NMR (COSY, NOESY, HSQC and HMBC), and by comparison with the literature data.     

Ellagitannin and flavonoid constituents from Agrimonia pilosa Ledeb. with their protein tyrosine phosphatase and acetylcholinesterase inhibitory activities

A new ellagitannin, agritannin (1), a new flavone glycoside, agriflavone (2), and another flavone glycoside with spectroscopic data reported for the first time, kaempferol-3-O-[(S)-3-hydroxy-3-methylglutaryl (1→6)]-β-d-glucoside (3), along with 16 known compounds were isolated from the aerial parts of Agrimonia pilosa Ledeb. These compounds were evaluated for PTP1B inhibitory activity. Among them, compounds 9 and 18 displayed potential inhibitory activity against PTP1B with IC₅₀ values of 7.14 ± 1.75 and 7.73 ± 0.24 μM, respectively. In addition, compound 1 showed significant inhibitory effect with an IC₅₀ value of 17.03 ± 0.09 μM. Furthermore, these compounds were tested in AChE inhibitory assays. Most of them were found to have moderate inhibitory effects, with IC₅₀ values ranging from 60.20 ± 1.09 to 92.85 ± 1.12 μM. Except compounds 3, 8, and 18 were inactive.     

New flavone and eudesmane derivatives from Lawsonia inermis and their inhibitory activity against NO production

A new flavone derivative, 7-hydroxy-3,5-dimethoxy-6,8-dimethylflavone (1) and a new eudesmane derivative, eudesmane-4β,7α-diol (2), have been isolated from the aerial part of Lawsonia inermis, together with ten known compounds (3–12). The structures of two new compounds were determined through spectroscopic and MS analyses. All compounds were evaluated for their inhibitory effects on Nitric Oxide production in LPS-stimulated RAW264.7 cells and compounds 3, 4, 6, 7, 9, and 10 showed inhibition with IC₅₀ values of 8.11, 2.32, 1.87, 7.72, 2.18, and 6.34 μg/mL, respectively.     

Bioactive acetophenones from Plectranthus venteri

In a project to investigate the chemistry of South African Plectranthus species, from the dichloromethane extract of the aerial parts of Plectranthus venteri, we isolated two known natural product acetophenones, namely 2-hydroxy-3,4,5,6-tetramethoxy-acetophenone (1) and 2-hydroxy-4,5,6-trimethoxy-acetophenone (2). Structures were assigned using NMR spectroscopy and HRTOFESIMS. Compound 1 was previously synthesised as a precursor to the polymethoxylated flavone nobiletin. The acetophenones exhibited remarkable inhibitory activities against the transfer of the IncW plasmid R7K in a bacterial plasmid transfer inhibition assay.     

Flavonoid diversification in different leaf compartments of Primula auricula (Primulaceae)

Populations of Primula auricula L. subsp. auricula from Austrian Alps were studied for flavonoid composition of both farinose exudates and tissue of leaves. The leaf exudate yielded Primula-type flavones, such as unsubstituted flavone and its derivatives, while tissue flavonoids largely consisted of flavonol 3-O-glycosides, based upon kaempferol (3, 4) and isorhamnetin (5–7). Kaempferol 3-O-(2″-O-β-xylopyranosyl-[6″-O-β-xylopyranosyl]-β-glucopyranoside) (3) and isorhamnetin 3-O-(2″-O-β-xylopyranosyl-[6″-O-β-xylopyranosyl]-β-glucopyranoside) (6) are newly reported as natural compounds. Remarkably, two Primula type flavones were also detected in tissues, namely 3′-hydroxyflavone 3′-O-β-glucoside (1) and 3′,4′-dihydroxyflavone 4′-O-β-glucoside (2), of which (1) is reported here for the first time as natural product. All structures were unambiguously identified by NMR and MS data. Earlier reports on the occurrence of 7,2′-dihydroxyflavone 7-O-glucoside (macrophylloside) in this species could not be confirmed. This structure was now shown to correspond to 3′,4′-dihydroxyflavone 4′-O-glucoside (2) by comparison of NMR data. Observed exudate variations might be specific for geographically separated populations. The structural diversification between tissue and exudate flavonoids is assumed to be indicative for different ecological roles in planta.     

Design and synthesis of aminoester heterodimers containing flavone or chromone moieties as modulators of P-glycoprotein-based multidrug resistance (MDR)

In this study, a new series of heterodimers was synthesized. These derivatives are N,N-bis(alkanol)amine aryl esters or N,N-bis(ethoxyethanol)amine aryl esters carrying a methoxylated aryl residue combined with a flavone or chromone moiety. The new compounds were studied to evaluate their P-gp modulating activity on a multidrug-resistant leukemia cell line. Some of the new compounds show a good MDR reversing activity; interestingly this new series of compounds does not comply with the structure-activity relationships (SAR) outlined by previously synthesized analogs carrying different aromatic moieties. In the case of the compounds described in this paper, activity is linked to different features, in particular the characteristics of the spacer, which seem to be critical for the interaction with the pump. This fact indicates that the presence of a flavone or chromone residue influences the SAR of these series of products, and that flexible molecules can find different productive binding modes with the P-gp recognition site. These results support the synthesis of new compounds that might be useful leads for the development of drugs to control P-gp-dependent MDR.     

Chemical constituents from Polygonatum odoratum

Twenty-two compounds, including five homoisoflavanones (1–3, 7 and 8), three isoflavones (9–11), flavone glycoside (19), one triterpenoid aglycon (5), two steroidal sapogenins (4, 6), five steroidal saponins (12, 13, 20–22), three lignanoids (14, 17 and 18) and two fatty acids (15 and 16) were isolated from the rhizomes of Polygonatum odoratum. The structures were elucidated by spectroscopic methods and by comparison of the reported spectral data. Additionally, the relationships between this plant and other species from Liliaceae family have also been discussed on the basis of the given compounds.     

A new methoxylated flavone from Lonicera hypoglauca and its chemotaxonomic significance

Phytochemical investigation of the stems and leaves of Lonicera hypoglauca Miq. led to the isolation of one novel methoxylated flavone, acunminatin (7,2′,4′-trihydroxyl-5,5′- methoxyflavone) (1), and fourteen known compounds (2–15), including six flavonoids (mearnsetin 2, kaempferol 3, acacetin 4, 5,7,3′,4′-tetramethoxyflavone 5, tricin 6, and 5,7,3′,4′,5′-pentamethoxyflavone 7), two coumarins (umbelliferone 8 and scopoletin 9), two phenylpropanoids (trans-ferulic acid 10 and chlorogenic acid 11), two iridoid glycosides (loganin 12 and sweroside 13), and two triterpenoids (uvaol 14 and ursolic acid 15). The structures of the compounds were identified by spectroscopic analysis and by comparing their spectral data with those reported in the literature. Five of these compounds (1, 2, 4, 5, and 7) were isolated from the L. genus for the first time, and compounds 6–8 and 14–15 were isolated for the first time from L. hypoglauca. The chemotaxonomic significance of the isolated compounds in the L. genus and the Caprifoliaceae family are discussed herein.     

Structural characteristics of flavanones and flavones from Cudrania tricuspidata for neuraminidase inhibition

The structural characteristics of flavonoids (1–3 and 6–8) from the root of Cudrania tricuspidata required for neuraminidase inhibition were studied and compared with commercially available flavonoids (4, 5, and 9–12). Alkylated flavanones (1–3) display better inhibition than the corresponding parent compound 4. Importantly, flavanone 1 bearing a C-8 hydrated prenyl group showed extremely high inhibition with IC₅₀ of 380 nM. On the other hand, the parent flavone 5 was more effective than alkylated analogues (6–8). Isolated inhibitors (1–3 and 6–8) showed noncompetitive inhibition in kinetic studies. The binding affinity of flavanones (1–4) for neuraminidase in in silico docking experiments correlated well with their IC₅₀ values and noncompetitive inhibition mode.     

A new flavone glycoside from the leaves of Agastache rugosa (Fisch. & C.A.Mey.) Kuntze

Agastache rugosa (Fisch. & C.A.Mey.) Kuntze has been widely used as a food spice and a remedy for colds in Korea, China and Japan. In this study, one new flavone glycoside (1) along with six flavonoids (2–7), nine phenyl glycosides (8–16) and three megastigmane glycosides (17–19) were isolated from the leaves of A. rugosa. By extensive spectroscopic methods including 1D and 2D NMR, and MS data, the structure of the new compound (1) was elucidated as acacetin 7-O-β-(6″-(E)-crotonylglucopyranoside). From present investigation, compound 1 and 7–19 were isolated for the first time from the genus Agastache and 1, 16, 18 and 19 in the Lamiaceae family.     

Antioxidant activity-guided isolation of flavonoids from Silene gallica aerial parts

A bio-guided fractionation of the 80% aqueous ethanolic extract of the aerial parts of Silene gallica L. (Caryophyllaceae), growing in North-Eastern Algeria, was performed to evaluate its antioxidant activity using DPPH, hydroxyl radical scavenging and CUPRAC assays. Successive chromatographic separations of the most antioxidant n-BuOH soluble fraction yielded four acylated flavone C-glycosides, vitexin 2''-O-β-d-(4''',6'''-di-acetyl)-glucopyranoside (1), orientin-2''-O-β-d-(4''',6'''-di-acetyl)-glucopyranoside (2), orientin-2''-O-β-d-(6'''-feruloyl)-glucopyranoside (3), and orientin-2''-O-β-d-(6'''-sinapoyl)-glucopyranoside (4), as well as six known compounds including four flavonoids (5-8), a phenylpropanoid glycerolglucoside (regaloside A) (9), and a phytoecdysteroide (20-hydroxyecdysone) (10). Their structures were established by UV, 1D, ²D NMR, and HR-ESI-MS spectral data, in addition to comparison with literature data. The antioxidant activity of the crude extracts, fractions and compounds 1-8 was evaluated. Two acylated orientin glycosides (3 and 4) displayed the strongest antioxidant activity.