Welwitschianalol A and B,two cyclohexene derivatives and other insecticidal constituents of Caesalpinia welwitschiana (Oliv.) Brenan

Crude methanol extract of the leaves of Caesalpinia welwitschiana was found to possess moderate larvicidal activity against second-instar larvae of Tuta absoluta Meyrick. Bioassay-guided fractionation of this extract led to the isolation of two oxygenated cyclohexene derivatives, welwitschianalol A (1, (1α,2β)-2-acetoxy-1-hydroxy-1- benzoyloxymethylcyclohex-5-ene) and B (2, (1α,2β)-2- benzoyloxy −1-cinnamoyloxymethyl-1-hydroxycyclohex-5-ene), together with eight known compounds, comprising bonducellin, dipteryxic acid, 3′-hydroxygenkwarin, afzelin, quercitrin, myricitrin, methyl gallate and gallic acid. The structures of the unknown compounds as well as those of the known ones were elucidated based on their MS, 1D and 2D NMR spectra, and in the case of known compounds, by comparison with the reported data. Each of welwitschianalol A and B, bonducellin, dipteryxic acid, afzelin, quercitrin and myricitrin showed more than 50% mortality of T. absoluta larvae at 5 ppm, which was comparable to that of azadirachtin (the most bioactive constituent of Azadirachta indica). The most potent constituent of C. welwitschiana was welwitschianalol B with LD₅₀ of 3.8 ppm, which was higher than that of azadirachtin (LD₅₀ of 7.8 ppm).     

Valproic acid induces three novel cytotoxic secondary metabolites in Diaporthe sp., an endophytic fungus from Datura inoxia Mill.

Addition of the valproic acid (histone deacetylases inhibitor) to a culture of an endophytic fungus Diaporthe sp. harbored from Datura inoxia significantly altered its secondary metabolic profile and resulted in the isolation of three novel compounds, identified as xylarolide A (1), diportharine A (2) and xylarolide B (3) along with one known compound xylarolide (4). The structures of all the compounds (1–4) were determined by detailed analysis of 1D and 2D NMR spectroscopic data. The relative configurations of compounds 1–3 were determined with the help of NOESY data and comparison of optical rotations with similar compounds with established stereochemistry. All the isolated compounds were screened for antibacterial, antioxidant and cytotoxic activities. Xylarolide A (1) and xylarolide (4) displayed significant growth inhibition of MIAPaCa-2 with an IC₅₀ of 20 and 32?µM respectively and against PC-3 with an IC₅₀ of 14 and 18?µM respectively. Moreover, compound 1 displayed significant DPPH scavenging activity with EC₅₀ of 10.3?µM using ascorbic acid as a positive control.     

Isoquinoline-derived alkaloids and one terpene lactone from the leaves of Duguetia pycnastera (Annonaceae)

The phytochemical investigation from the leaves of Duguetia pycnastera Sandwith (Annonaceae) led to the isolation and identification of ten compounds: nine isoquinoline-derived alkaloids, including five aporphines, anonaine, isopiline, O-methylisopiline, nornuciferine, and norstephalagine; three oxoaporphines, O-methylmoschatoline, liriodenine, and lysicamine; and one tetrahydroprotoberberine, isocorypalmine; in addition, one C₁₁-terpene lactone known as loliolide. The isolated compounds (except for O-methylmochatoline and lysicamine) are described for the first time in the species and their chemophenetics relationships were discussed. The occurrence of loliolide is reported for the first time in the Duguetia. The structure elucidation of these compounds was established by extensive analyzes of 1D and 2D NMR spectroscopy in combination with MS. The NMR spectroscopic data for norstephalagine and isocorypalmine were reviewed.     

Phytochemical study of Stachys candida Bory & Chaubard (Lamiaceae)

Phytochemical analysis of the aerial parts of Stachys candida Bory & Chaubard, growing wild in Greece led to the isolation of eleven bioactive secondary metabolites. Nine flavones, one of them methylated, one phenylethanoid glycoside and one phenolic acid were isolated from the methanol extract of this plant. The structure elucidation of the isolated compounds was achieved on the basis of NMR spectroscopy (1D and 2D spectra). The phytochemical profile was appeared to be similar with other Greek endemic Stachys species, while a strong difference was the absence of iridoids. Importantly, the chemotaxonomic significance of the isolated compounds has extensively been described.     

Cytotoxic triterpenoid saponins from the stem bark of Antonia ovata

Phytochemical investigation of the MeOH extract of the stem bark of Antonia ovata led to the isolation of four triterpenoid saponins, along with eleven known compounds. Their structures were established by extensive 1D and 2D NMR, as well as HR-MS analysis and acid hydrolysis. All isolated saponins contained the same tetrasaccharide chain O-β-d-xylopyranosyl-(1 → 2)-O-β-d-glucopyranosyl-(1 → 3)-O-[β-d-glucopyranosyl-(1 → 2)]-β-d-glucuropyranoside linked to C-3 of esterified derivatives of R₁-barrigenol, A₁-barrigenol, barringtogenol C, or camelliagenin. Biological evaluation of the compounds against KB cell line revealed a potent cytotoxic activity with IC₅₀ values ranging from 3.1 to 6.6 μM. The known compounds were found to be inactive at 10 μg/ml concentration.     

Lignan derivatives from Selaginella tamariscina and their nitric oxide inhibitory effects in LPS-stimulated RAW 264.7 cells

The chemical characterization of Selaginella tamariscina leaves resulted in the isolation of five lignanoside derivatives (1–4 and 6) and one neolignan (5). These compounds include three new lignanosides, tamariscinosides D–F (1–3), and one liriodendrin (4) that were isolated for the first time from this plant, together with two known compounds, (2R,3S)-dihydro-2-(3,5-dimethoxy-4-hydroxyphenyl)-7-methoxy-5-acetyl-benzofuran (5) and moellenoside B (6). The chemical structures of these isolated compounds were determined using 1D and 2D NMR, MS, and CD spectroscopic data, and the results were compared to data previously reported in the literatures. These compounds were also evaluated in terms of their inhibition of NO production in lipopolysaccharide (LPS)-stimulated activity in the macrophage cell line RAW 264.7. Among them, compounds 1, 2, 5, and 6 exhibited a significant inhibition with IC₅₀ values ranging from 32.3 to 55.8 μM.     

Aldose reductase inhibitory compounds from extracts of Dipsacus asper

Amethanolic extract of Dipsacus asper, having anti-diabetic activity, was examined as a possible aldose reductase (ALR2) inhibitor, a key enzyme involved in diabetic complications. Bioactivity guided fractionation led to the isolation of ten compounds, ursolic acid (1), oleanolic acid-3-O-α-L-arabinopyranoside (2), daucosterol (3), hederagenin-3-O-α-L-arabinopyranoside (4), sweroside(5), caffeic acid (6), esculetin (7), protocatechualdehyde (8), loganin (9), and vanilic acid (10) from the ethyl acetate fraction of D. asper methanol extract. Among them, compounds 4, 6, 7, and 8 exhibited inhibitory effects on aldose reductase, with IC₅₀ values of 23.70, 16.71, 34.36, and 21.81 μM, respectively. This is the first report on the isolation of these compounds from D. asper, and the ALR2 inhibitory activity of hederagenin-3-O-α-L-arabinopyranoside. These results suggest the successful use of the extract of D. asper for ameliorating diabetic complications.     

Chemical constituents of the medicinal plant Indigofera spicata Forsk (Fabaceae) and their chemophenetic significance

The chemical investigation of the whole plant of Indigofera spicata Forsk (Fabaceae), a medicinal plant from Cameroon, resulted in the isolation of a new benzofuran, named spibenzofuran (1a), together with ten known secondary metabolites including one benzofuran (2), one flavonoid (3), one saponin (6), two triterpenes (4 and 5), two steroids (8 and 11), one phthalate (7) and two fatty acids (9 and 10). All these compounds have been isolated for the first time from this plant. The structures of the isolated compounds were established by spectroscopic analysis including HR-ESI-MS, 1D and 2D NMR and by comparison of our data with the reported data. The isolated compounds might be considered as the chemophenetic markers of this species, and antibacterial and urease inhibitory activities of some isolated compounds were assessed.     

Biflavonoids from Fumana procumbens (Dunal) Gren. & Godr

The first phytochemical investigation on the aerial parts of Fumana procumbens (Dunal) Gren. & Godr. led to the isolation and identification of six compounds, including two biflavonoids, i.e. dihydrodaphnodorin B (1) and daphnodorin B (2); three flavonoids, i.e. quercitrin (3), myricitrin (4), and quercetin (5); and a flavan derivative, i.e. epigallocatechin (6). The structures of the compounds were elucidated by extensive 1D- and 2D-NMR spectroscopic analysis in combination with MS experiments. This is the first report on the isolation of biflavonoids from the genus Fumana and from the family Cistaceae.     

Alkamides and a neolignan from Echinacea purpurea roots and the interaction of alkamides with G-protein-coupled cannabinoid receptors

Multiple chromatographic separations of the CHCl₃-soluble extract of the roots of Echinacea purpurea led to the isolation of 19 compounds. Four natural products, three alkamides and nitidanin diisovalerianate, were identified, and five further compounds were detected for the first time in this species. Additionally, 10 known E. purpurea metabolites were isolated. The structures were determined by mass spectrometry and advanced 1D and 2D NMR techniques. The bioactivity of the isolated compounds was studied in [³⁵S]GTPγS-binding experiments performed on rat brain membrane preparations. Both partial and inverse agonist compounds for cannabinoid (CB1) receptors were identified among the metabolites, characterized by weak to moderate interactions with the G-protein signaling mechanisms. The G-protein-modulating activities of the Echinacea compounds are rather far from the full agonist effects seen with the CB1 receptor agonist reference compound arachidonyl-2′-chloroethylamide (ACEA). However, upon coadministration with ACEA, a number of them proved capable of inhibiting the stimulation of the pure agonist, thereby demonstrating cannabinoid receptor antagonist properties.     

Triterpene hexahydroxydiphenoyl esters and a quinic acid purpurogallin carbonyl ester from the leaves of Castanopsis fissa

Triterpene hexahydroxydiphenoyl (HHDP) esters have only been isolated from Castanopsis species, and the distribution of these esters in nature is of chemotaxonomical interest. In this study, the chemical constituents of the leaves of Castanopsis fissa were examined in detail to identify and isolate potential HHDP esters. Together with 53 known compounds, 3,4-di-O-galloyl-1-O-purpurogallin carbonyl quinic acid (1) and 3,24-(S)-HHDP-2α,3β,23,24-tetrahydroxytaraxastan-28,20β-olide (2) were isolated and their structures were elucidated by spectroscopic and chemical methods. The polyphenols of the leaves were mainly composed of galloyl quinic acids, triterpenes HHDP esters, ellagitannins and flavonol glycosides. In particular, the isolation yields of 1,3,4-trigalloyl quinic acid and compound 2 were 1.53% and 0.27%, respectively, from the fresh leaves. The presence of lipid soluble HHDP esters of oleanane-type triterpenes as one of the major metabolites is an important chemotaxonomical discovery. Lipase inhibition activities and ORAC values of the major constituents were compared. The triterpene HHDP ester showed moderate lipase inhibition activity and myricitrin gave the largest ORAC value.     

Ehrenasterol and biemnic acid; new bioactive compounds from the Red Sea sponge Biemna ehrenbergi

In continuation of our efforts to identify bioactive compounds from the Red Sea marine sponges, we have recently investigated the organic extract of the sponge Biemna ehrenbergi. This study resulted in the isolation of eight compounds including a new sterol, ehrenasterol (1), a new C₂₄-acetylenic acid, biemnic acid (2), together with six known compounds including a hopanoid, three steroids and two nucleosides. The isolated compounds were identified as (22E)-ergosta-22-ene-8,14-epoxy-3,7-dione (1), (E)-tetracos-8-en-5-ynoic acid (2), (22E)-ergosta-5,8,22-trien-7-one-3β-ol (3), 32,35-anhydrobacteriohopanetetrol (4), (24R)-ergosta-6,22-diene-5,8-epidioxy-3-ol (5), melithasterol B (6), thymidine (7) and 2′-deoxyuridine (8). The structures of the isolated compounds were assigned by different spectral data including 1D and 2D NMR (COSY, HSQC, and HMBC) and high-resolution mass spectrometry. Compound 1 displayed inhibition zone of 20 mm at 100 μg/disc against Escherichia coli in the disc diffusion assay. Similarly, compounds 2 and 4 displayed inhibition zones of 20 and 18 mm respectively against Candida albicans at the same concentration. Compounds 1–3 displayed weak cytotoxic activity against human colon adenocarcinoma (HCT-116) cancer cell line.     

Antiviral isoindolone derivatives from an endophytic fungus Emericella sp. associated with Aegiceras corniculatum

Chemical investigation of the endophytic fungus Emericella sp. (HK-ZJ) isolated from the mangrove plant Aegiceras corniculatum led to isolation of six isoindolones derivatives termed as emerimidine A and B and emeriphenolicins A and D, and six previously reported compounds named aspernidine A and B, austin, austinol, dehydroaustin, and acetoxydehydroaustin, respectively. Their structures were elucidated on the basis of NMR spectroscopic evidence while the anti-influenza A viral (H₁N₁) activities of eight compounds were also evaluated using the cytopathic effect (CPE) inhibition assay.     

Phytochemical and chemotaxonomic investigation from the roots of Anemone vitifolia Buch.-Ham. (Ranunculaceae)

Phytochemical investigation from the roots of Anemone vitifolia Buch.-Ham. led to the isolation of eight compounds, including one triterpenoid saponin, two sugars, one coumarin, one amide, one saturated alkane, one olefin and one fatty acid. The structures of these metabolites were elucidated by spectroscopic data and comparisons with the data available in the literature. Among them, compound 7 ((6Z,9Z,12Z)-6,9,12-Eicosatriene) was isolated for the first time as a natural product. Furthermore, compounds 2 (D-(+)-raffinose), 3 (mixture of β-D-fructopyranose and β-D-fructofuranose) and 5 (bonaroside) were obtained from the Ranunculaceae family for the first time. Compounds 4 (siderin) and 6 (n-hexadecane) were isolated from A. vitifolia for the first time. The chemotaxonomic significance of the isolated compounds was discussed.     

New 19α-hydroxyursane-type triterpenes from the leaves of Meyna spinosa (= Vangueria spinosa), Rubiaceae

Two new 19α-hydroxyursane-type triterpenes, 2α,3α,19α,24,28-pentahydroxyurs-12-ene (1) and meyanthic acid, 3β-acetoxy-2β,19α,23-trihydroxyurs-12-en-28-oic acid (2) along with one new aliphatic ester, myricyl pentadecanoate (3) and five known compounds, 19α-hydroxyasiatic acid (4), oleanolic acid (5), myricyl alcohol (6), β-sitosterol (7) and its glycoside (8) were isolated from the methanolic leaf extract of Meyna spinosa Roxb. ex Link (= Vangueria spinosa Roxb., Rubiaceae). The structures of the new compounds were elucidated on the basis of extensive spectroscopic (including 2D NMR) analysis and comparison with literature. Except oleanolic acid, isolation of known compounds was reported for the first time from this plant.     

Bioactivity-guided isolation of chemical constituents against H2O2-induced neurotoxicity on PC12 from Cimicifuga dahurica (Turcz.) Maxim.

Three new compounds (1, 6, 9), with six known compounds (2–5, 7–8) were obtained from water-soluble extract of Cimicifuga dahurica (Turcz.) Maxim. by bioactivity-guided isolation. Their structures were elucidated by chemical and spectral analysis, including 1D, 2D NMR data and HRESIMS. H₂O₂-induced neurotoxicity on PC12 cells model were conducted to evaluate the neuro-protective capability of these compounds. The piscidic acid derivatives compounds 4–7 showed marked neuro-protective effect at certain concentration.     

New secondary metabolites from Dodonaea viscosa

Bioassay guided fractionation and chemical investigation of the ethanolic extract of the aerial parts of Dodonaea viscosa Linn. from Egypt, resulted in the isolation and identification of three new compounds, including two new clerodane diterpenoids 1 and 2 and a new myo-inositol derivative 3, along with nine known compounds 4–12. The structures of the isolated compounds were elucidated using 1D and 2D NMR experiments, HRESIMS, and comparison with literature data. All isolated compounds were evaluated for their antibacterial, antifungal, antimalarial as well as antileishmanial activities. Compound 5 exhibited good antifungal activity against Cryptococcus neoformans with an IC₅₀ value of 6.11 μg/ml. Compounds 10 and 12 showed moderate antileishmanial activity against Leishmania donovani with IC₅₀ values of 16.6 and 19.06 μg/ml, respectively.     

A new triterpenoid and other constituents from Lepidogrammitis drymoglossoides

Phytochemical investigation of a Chinese fern Lepidogrammitis drymoglossoides led to the isolation of five compounds, including one triterpenoid, two lignans and two glycosides. Their structures were determined to be filic-3-ene-28-oic acid (1), (−)-syringaresinol-4-O-beta-d-glucopyranoside (2), lyoniresinol (3), 4-O-beta-d-glucopyranosyl caffeic acid (4) and n-butyl-O-beta-d-fructopyranoside (5) on the basis of mass and NMR spectra and chemical and physical properties. Filic-3-ene-28-oic acid (1) is a new triterpenoid, while compounds 2–5 were isolated from the genus Lepidogrammitis for the first time. Chemotaxonomic significance of this investigation is summarized.     

New flavone-di-C-glycosides from the seeds of Egyptian lupin (Lupinus termis)

Raw lupin seeds flour is increasingly used as a food ingredient because of its nutritional and functional values. This study is considered to be the first phytochemical investigation of the flavonoids of the methanol (MeOH) fraction of Lupinus termis seeds. The study led to the isolation of two new di-C-glycoside flavones, apigenin-6-C-β-d-glucopyranosyl-8-C-[β-d-apiofuranosyl-(1 → 2)]-β-glucopyranoside (1), apigenin-6-C-β-d-glucopyranosyl-8-C-[α-l-rhamnopyranosyl-(1 → 2)]-β-glucopyranoside (2), together with one known flavone di-C-glycoside, apigenin-7-O-β-d-apiofuranosyl-6,8-di-C-β-glucopyranoside (3). These compounds are considered to have potential functional properties. The isolated compounds may contribute to the yellow color of raw lupin seeds flour-based products. It may also be used as natural yellow color in food or pharmaceutical products and as a dietary supplement product. These rare flavones were purified by using semi-preparative HPLC. The structures of the isolated compounds were elucidated on the basis of extensive spectroscopic methods, 1D and 2D nuclear magnetic resonance techniques, FAB (Fast Atom Bombardment) – mass spectrometry and acid hydrolysis.     

Steroidal saponins and homoisoflavanone from the aerial parts of Sansevieria cylindrica Bojer ex Hook.

Phytochemical study on the methanolic extract of Sansevieria cylindrica aerial parts lead to the isolation, characterization and structure elucidation of a new steroidal saponin, 1β-hydroxy-kryptogenin-1-O-α-l-rhamnopyranosyl-(1 → 2)-α-l-arabinopyranoside (1), a new homoisoflavanone, (3S)-3,7-dihydroxy-8-methoxy-3-(3′,4′-methylenedioxybenzyl) chroman-4-one (2) and the known saponin alliospiroside A (3). To the best of our knowledge, the genin 1β-hydroxy-kryptogenin is reported here for the first time. The structures of the new compounds were determined by UV, IR, EIMS, HRESIMS together with 1D (¹H and ¹³C) and 2D (HSQC and HMBC) NMR spectral analysis. The isolated compounds 1–3 were tested for their radical scavenging activity (DPPH). Compound 2 exhibited activity compared to that of ascorbic acid as a standard. The cytotoxicity of the isolated compounds and the standard doxorubicin was tested against the three human tumor cell lines HT116, MCF-7 and PC-3. The results showed that the isolated compounds were inactive.