Prenyl Pterocarpans from Algerian Bituminaria bituminosa and Their Effects on Neuroblastoma.

The pterocarpan fraction from aerial parts of Bituminaria bituminosa was investigated for both chemical characterization and biological evaluation. Chemical studies were in accordance with the literature data on Bituminaria genus resulting in the identification of typical 4,8-prenyl pterocarpans. Three new members, bituminarins A-C (1-3), were isolated along with main bitucarpin A (4), erybraedin C (5) and erybraedin D (6) already reported from this plant. Further, biological studies evidenced antiproliferative properties of the most abundant pterocarpans 4 and 5 on neuroblastoma SH-SY5Y cell line, in agreement with previously described antiproliferative activity of these compounds against cancer cell lines other than neuroblastoma. The structure and the stereochemistry of the new molecules was determined by extensive spectroscopic analysis and chemical derivatization methods. The biological investigation was carried out by using an assay platform based on a live-cell imaging system revealing an apoptotic cell death induction.

New Compounds from the Roots of Corsican Calicotome Villosa (Poir.) Link.: Two Pterocarpans and a Dihydrobenzofuran.

Three new compounds, a dihydrobenzofuran (coumaran) derivative (compound 1) and two pterocarpans (compounds 2 and 3) were isolated from a root extract of Calicotome villosa growing wild in Corsica. Their structures were elucidated using 1D and 2D NMR spectroscopy and MS/MS as 2-(1-methylethenyl)-5-hydroxy-6-carbomethoxy-2,3-dihydro-benzofuran, 4,9-dihydroxy-3-methoxy-2-dimethylallylpterocarpan, and 4,9-dihydroxy-3',3'-dimethyl-2,3-pyranopterocarpan.

Antidepressant Potential of Lotus corniculatus L. subsp. corniculatus: An Ethnobotany Based Approach.

As a Turkish traditional medicinal plant, aerial parts of Lotus corniculatus L. subsp. corniculatus (Fabaceae) are used as a painkiller, antihemoroidal, diuretic and sedative. In this study, the antidepressant potential of the plant has been attempted to clarify. Extracts with water, n-Hexane, ethyl acetate, and methanol were prepared respectively from the aerial parts. Antidepressant activity of the extracts were researched by using three different in vivo test models namely a tail suspension test, antagonism of tetrabenazine-induced hypothermia, ptosis, and suppression of locomotor activity and forced swimming test on male BALB/c mice and in vitro monoamine oxidase (MAO)-A and B inhibition assays. The results were evaluated through comparing with control and reference groups, and then active compounds of the active extract have been determined. Bioassay-guided fractionation of active fraction led to the isolation of three compounds and structures of the compounds were elucidated by spectroscopic methods. The data of this study demonstrate that the MeOH extract of the aerial parts of the plant showed remarkable in vivo antidepressant effect and the isolated compounds medicarpin-3-O-glucoside, gossypetin-3-O-glucoside and naringenin-7-O-glucoside (prunin) from the active sub-fractions could be responsible for the activity. Further mechanistic and toxicity studies are planned to develop new antidepressant-acting drugs.

Antiproliferative Pterocarpans and Coumestans from Lespedeza bicolor.

Chromatographic purification of a methanol extract of the roots of Lespedeza bicolor led to the isolation of four new pterocarpans (1-4), two new coumestans (6 and 7), two new arylbenzofurans (8 and 9), and the known pterocarpan 1-methoxyerythrabyssin II (5). Their structures were identified using NMR spectroscopy, UV spectroscopy, and mass spectrometry. Cytotoxicity assays showed that compounds 1-9 exerted antiproliferative effects on blood cancer cells. Of these compounds, 1 and 6 induced mitochondrial depolarization and induced apoptosis in Jurkat cells. These compounds promoted cell death by inducing cell-cycle arrest at the G1 stage, reducing levels of BCL2, and increasing cleavage of PARP-1. These findings indicate that 1 and 6 are possible lead compounds for the treatment of human leukemia cells via intracellular signaling.

Extraction of biomedical compounds from the wood of Pterocarpus macarocarpus Kurz heartwood.

Some wood can be used as traditional Chinese medicine. The medicinal value of wood is associated with its extractives. Pterocarpus macarocarpus Kurz heartwood is a kind of top valuable reddish hardwood in making furniture and handicrafts, but the research about medicine value of this wood is not enough. In order to investigate the high value biomedical compounds in Pterocarpus macarocarpus Kurz heartwood, the woody extractives were obtained by Soxhlet extraction and ultrasonic extraction with benzene-ethanol (1:2, v/v) solvent simultaneously and were analyzed by Gas Chromatography-Mass Spectrometer (GC-MS). Combining with the results of the two extraction methods, 44 compounds can be identified in total. Amony these identified compounds, there were 5 flavonoids, 15 terpenes and 3 steroidal compounds. The representative biomedical compositions were homopterocarpin, medicarpin, (-)-pterocarpin, formononetin, ß-eudesmol, stigmasterol, linoleic acid and so on, which indicated that the extractives from Pterocarpus macarocarpus Kurz heartwood have huge potential in biomedicine. This research provides scientific basis for further comprehensive utilization of Pterocarpus macarocarpus Kurz heartwood as Chinese medicine.

Sophopterocarpan A, a novel pterocarpine derivative with a benzotetrahydrofuran-fused bicyclo [3.3.1] nonane from Sophora flavescens.

Sophopterocarpan A (1), with a novel benzotetrahydrofuran-fused bicyclo [3.3.1] nonane ring, was isolated from the roots of Sophora flavescens Ait. Its unusual structure, including its stereochemistry, was determined on the basis of a comprehensive spectroscopic data analysis. A plausible biogenetic pathway for 1 is presented. Sophopterocarpan A was identified as a potential autophagy activator. Additionally, it was found that 1 exhibited cytotoxic activity in MCF-7 cells with an IC50 of 29.36 µM.

Preparative chiral separation and absolute configuration of the synthetic pterocarpanquinone LQB-118.

The racemic pterocarpanquinone LQB-118 is active, in mice and hamsters, against tegumentary and visceral leishmaniasis. This compound also presents antiinflammatory and antineoplastic activity in mice. The low level of toxicity observed in these studies makes LQB-118 a promising drug candidate. In order to conduct further biological testing to investigate enantioselectivity in the above-mentioned activities, a multimilligram amount of each enantiomer of LQB-118 was produced. Furthermore, vibrational circular dichroism (VCD) and Density Functional Theory (DFT) calculations were used to determine unambiguously their absolute configurations. The comparison of experimental and calculated VCD data led to the assignment of (-)-LQB-118 as 7aR,12aR and, consequently, (+)-LQB-118 as 7aS12aS.

Superbanone, A New 2-Aryl-3-benzofuranone and Other Bioactive Constituents from the Tube Roots of Butea superba.

Phytochemical investigation from the tube roots of Butea superba, led to the isolation and identification of a new 2-aryl-3-benzofuranone named superbanone (1), one benzoin, 2-hydroxy-1-(2-hydroxy-4-methoxyphenyl)-2-(4-methoxyphenyl)ethanone (2), eight pterocarpans (3 - 10), and eleven isoflavonoids (11 - 21). Compound 2 was identified for the first time as a natural product. The structure of the isolated compounds was elucidated using spectroscopic methods, mainly 1D- and 2D-NMR. The isolated compounds and their derivatives were evaluated for α-glucosidase inhibitory and antimalarial activities. Compounds 3, 7, 8, and 11 showed promising α-glucosidase inhibitory activity (IC50  = 13.71 ± 0.54, 23.54 ± 0.75, 28.83 ± 1.02, and 12.35 ± 0.36 µm, respectively). Compounds 3 and 11 were twofold less active than the standard drug acarbose (IC50  = 6.54 ± 0.04 µm). None of the tested compounds was found to be active against Plasmodium falciparum strain 94. On the basis of biological activity results, structure-activity relationships are discussed.

Antiplasmodial Isoflavanes and Pterocarpans from Apoplanesia paniculata.

Bioassay-guided fractionation of an EtOH extract of the roots of the plant Apoplanesia paniculata (Fabaceae) led to the isolation of the three known compounds amorphaquinone (1), pendulone (2), and melilotocarpan C (3), and the two new pterocarpans 4 and 5. Compounds 1 and 2 exhibited good antiplasmodial activity with IC50 values of 5.7 ± 1.5 and 7.0 ± 0.8 µM, respectively. Compound 3 exhibited weak antiplasmodial activity (41.8 ± 5.2 µM), while compounds 4 and 5 were inactive. Compound 6 was synthesized to confirm the structure of 5, and it showed enhanced antiplasmodial activity (15.8 ± 1.4 µM) compared to its analogues 3-5.

Pyrano-isoflavans from Glycyrrhiza uralensis with antibacterial activity against Streptococcus mutans and Porphyromonas gingivalis.

Continuing investigation of fractions from a supercritical fluid extract of Chinese licorice (Glycyrrhiza uralensis) roots has led to the isolation of 12 phenolic compounds, of which seven were described previously from this extract. In addition to these seven metabolites, four known components, 1-methoxyerythrabyssin II (4), 6,8-diprenylgenistein, gancaonin G (5), and isoglycyrol (6), and one new isoflavan, licorisoflavan C (7), were characterized from this material for the first time. Treatment of licoricidin (1) with palladium chloride afforded larger amounts of 7 and also yielded two new isoflavans, licorisoflavan D (8), which was subsequently detected in the licorice extract, and licorisoflavan E (9). Compounds 1-9 were evaluated for their antibacterial activities against the cariogenic Streptococcus mutans and the periodontopathogenic Porphyromonas gingivalis. Licoricidin (1), licorisoflavan A (2), and 7-9 showed antibacterial activity against P. gingivalis (MICs of 1.56-12.5 µg/mL). The most potent activity against S. mutans was obtained with 7 (MIC of 6.25 µg/mL), followed by 1 and 9 (MIC of 12.5 µg/mL). This study provides further evidence for the therapeutic potential of licorice extracts for the treatment and prevention of oral infections.

Fusarium graminearum Possesses Virulence Factors Common to Fusarium Head Blight of Wheat and Seedling Rot of Soybean but Differing in Their Impact on Disease Severity.

Fusarium graminearum is a toxigenic fungal pathogen that causes Fusarium head blight (FHB) and crown rot on cereal crops worldwide. This fungus also causes damping-off and crown and root rots at the early stage of crop development in soybean cultivated in North and South America. Several F. graminearum genes were investigated for their contribution to FHB in cereals but no inherent study is reported for the dicotyledonous soybean host. In this study we determined the disease severity on soybean seedlings of five single gene disrupted mutants of F. graminearum, previously characterized in wheat spike infection. Three of these mutants are impaired on a specific function as the production of deoxynivalenol (DON, Δtri5), lipase (ΔFgl1), and xylanase (Δxyl03624), while the remaining two are MAP kinase mutants (ΔFgOS-2, Δgpmk1), which are altered in signaling pathways. The mutants that were reduced in virulence (Δtri5, ΔFgl1, and ΔFgOS-2) or are avirulent (Δgpmk1) on wheat were correspondently less virulent or avirulent in soybean seedlings, as shown by the extension of lesions and seedling lengths. The Δxyl03624 mutant was as virulent as the wild type mirroring the behavior observed in wheat. However, a different ranking of symptom severity occurred in the two hosts: the ΔFgOS-2 mutant, that infects wheat spikelets similarly to Δtri5 and ΔFgl1 mutants, provided much reduced symptoms in soybean. Differently from the other mutants, we observed that the ΔFgOS-2 mutant was several fold more sensitive to the glyceollin phytoalexin suggesting that its reduced virulence may be due to its hypersensitivity to this phytoalexin. In conclusion, lipase and DON seem important for full disease symptom development in soybean seedlings, OS-2 and Gpmk1 MAP kinases are essential for virulence, and OS-2 is involved in conferring resistance to the soybean phytoalexin.

α-Glucosidase inhibitory activities of isoflavanones, isoflavones, and pterocarpans from Mucuna pruriens.

Three new isoflavanones (1-3) and thirteen known compounds (4-16) were isolated from the roots of Mucuna pruriens. The absolute configurations of isoflavanones 1-3 and parvisoflavanone (4), lespedeol C (5), and uncinanone C (6) were addressed by a circular dichroism technique. Isoflavanones, isoflavones, and pterocarpans of M. pruriens were found to be α-glucosidase inhibitors. Medicarpin (7) and parvisoflavone B (9) were potent α-glucosidase inhibitors (twofold less active than the standard drug acarbose). The production of bioactive metabolites in M. pruriens seems to be season-dependent.

[Chemical constituents of Dalbergia odorifera].

Fourteen compounds were isolated from Dalbergia odoriferae and purified by repeated column chromatography on silica and sephadex LH-20 gel and structurally identified by spectral analysis. These compounds were identified as 4, 9-dimethoxy-3-hydroxypterocarpan (1), medicarpin (2), 2', 4', 5-trihydroxy-7-methoxyisoflavone (3), 2', 3', 7-trihydroxy-4'-methoxyisoflavan (4), formononetin (5), 3, 8-dihydroxy-9-methoxypterocarpan (6), koparin (7), 3-hydroxy-9-methoxypterocarp-6a-ene (8), 2'-hydroxyformononetin (9), stevenin (10), 2', 7-dihydroxy-4', 5'-dimethoxyisoflavone (11), lyoniresinol (12), 2, 4-dihydroxy-5-methoxy-benzophenone (13) and neokhriol A (14). Compounds 1, 3, 4, 6, 8, 12 and 14 were isolated from this plant for the first time. Antibacterial activity assay showed that compound 4 had inhibitory effect on Ralstonia solanacearum.

[Hepatoprotective properties of isoflavonoids from roots of Maackia amurensis on experimental carbon tetrachloride-induced hepatic damage].

Hepatoprotective properties of ethanol extract from the roots of Maackia amurensis Ruper et Maxim have been studied on the model of toxic hepatitis induced by carbon tetrachloride damage. It is established that the extract contains daidzein, 7-O-gentobiosides of isoflavonoids genistein, formononetin, pseudobabtige-nin, and 5-O-methylgenistein, and 3-O-gentobiosides of pterocarpans (6aR, 11aR)-maakiain and (6aR, 11aR)-medicarpin. The administration of extract facilitates the restoration of antioxidant protection enzymes activity and reduced glutathione level, decreases the formation of toxic peroxidation products, produces normalizing impact on liver phospholipid pattern, and improves the erythrocyte tolerance to hemolytic agents. The action of isoflavonoids from Maackia amurensis in restoration of metabolic pathways of the liver and removal of toxic stress was more effective as compared to that of the reference hepatoprotector legalon.

[Chemical constituents from aerial part of Rumex patientia].

OBJECTIVE: To study the chemical constituents from aerial part of Rumex patientia. METHODS: The compounds were isolated and purified by silica gels and polyamide column chromatography. Their structures were elucidated by physicochemical and spectroscopic evidences. RESULTS: Twelve compounds were identified as: chrysophanol (1), chrysophanol-8-O-beta-D-glucopyranoside (2), physcion (3), emodin(4), emodin-8-O-beta-D-glucopyranoside (5), maackiain (6), maackiain-3-O-beta-D-glucopyranoside (7), quercetin-3-O-beta-D-glucopyranoside (8), quercetin-3-O-beta-D-glucuronide(9), 2-O-methylinositol (10), torachrysone-8-O-beta-D-glucopyranoside (11) and nepodin-8-O-beta-D-glucopyranoside (12). CONCLUSION: Compounds 6, 7, 10 are isolated from this genus for the first time, and compound 9 is isolated from this plant for the first time.

Cytotoxic evaluation of alkaloids and isoflavonoids from the Australian tree Erythrina vespertilio.

A new glucoalkaloid, vespertilioside, together with three known alkaloids, including 11- ß-methoxyglucoerysovine, erysotrine, and hypaphorine, were isolated from the fruits of E. vespertilio Benth. In addition, three known isoflavonoids, including phaseollin, alpiniumisoflavone, and phaseollidin, were identified from the plant stems. The structures of compounds were determined by 1D/2D NMR and mass experiments. The cytotoxic activity of all compounds was evaluated against a metastatic prostate cancer cell line (PC3) and neonatal foreskin fibroblast (NFF) using a real-time label-free cell analyser. Among the tested compounds, phaseollidin showed cytotoxic activities against PC3 (IC (50) = 8.83 ± 1.87 µM) and NFF (0.64 ± 0.37 µM) cell lines.

Potent inhibition of bacterial neuraminidase activity by pterocarpans isolated from the roots of Lespedeza bicolor.

Bacterial neuraminidase has been highlighted as a key enzyme for pathogenic infection and sepsis. Six pterocarpans displaying significant levels of neuraminidase inhibitory activity were isolated from the root bark of Lespedeza bicolor. The isolated compounds were identified as three new pterocarpans (1-3) together with known compounds erythrabyssin II (4), lespebuergine G4 (5), and 1-methoxyerythrabyssin II (6). The new compounds were characterized as bicolosin A (1), bicolosin B (2), and bicolosin C (3). All compounds inhibited bacterial neuraminidase in a dose-dependent manner with significant inhibition (IC(50)=0.09-3.25 µM). All neuraminidase inhibitors screened were found to exhibit noncompetitive kinetics. The three most potent neuraminidase inhibitors (1, 3 and 6) feature a methoxy substitution on C-1.

Estrogenic activity of chemical constituents from Tephrosia candida.

In a continued investigation of medicinal plants from the genus Tephrosia, phytochemical analysis of a methylene chloride-methanol (1:1) extract of the air-dried aerial parts of Tephrosia candida afforded two new 8-prenylated flavonoids, namely, tephrocandidins A (1) and B (2), a new prenylated chalcone, candidachalcone (3), a new sesquiterpene (4), and a previously reported pea flavonoid phytoalexin, pisatin (5). The structures of 1-4 were established by spectroscopic methods, including HREIMS, and 1H, 13C, DEPT, HMQC, and HMBC NMR experiments. The most potent estrogenic activity of these isolated natural products in an estrogen receptor (ERα) competitive-binding assay was for 3, which exhibited an IC50 value of 80 µM, compared with 18 nM for the natural steroid 17ß-estradiol. Results were interpreted via virtual docking of isolated compounds to an ERα crystal structure.

Isoflavonoids and coumarins from Glycyrrhiza uralensis: antibacterial activity against oral pathogens and conversion of isoflavans into isoflavan-quinones during purification.

Phytochemical investigation of a supercritical fluid extract of Glycyrrhiza uralensis has led to the isolation of 20 known isoflavonoids and coumarins, and glycycarpan (7), a new pterocarpan. The presence of two isoflavan-quinones, licoriquinone A (8) and licoriquinone B (9), in a fraction subjected to gel filtration on Sephadex LH-20 is due to suspected metal-catalyzed oxidative degradation of licoricidin (1) and licorisoflavan A (2). The major compounds in the extract, as well as 8, were evaluated for their ability to inhibit the growth of several major oral pathogens. Compounds 1 and 2 showed the most potent antibacterial activities, causing a marked growth inhibition of the cariogenic species Streptococcus mutans and Streptococcus sobrinus at 10 µg/mL and the periodontopathogenic species Porphyromonas gingivalis (at 5 µg/mL) and Prevotella intermedia (at 5 µg/mL for 1 and 2.5 µg/mL for 2). Only 1 moderately inhibited growth of Fusobacterium nucleatum at the highest concentration tested (10 µg/mL).

[Chemical constituents of Ammopiptanthus mongolicus].

OBJECTIVE: To study the chemical constituents of aerial parts of Ammopiptanthus mongolicus. METHOD: Isolation and purification were carried out on silica gel, Sephadex LH-20 and HPLC column chromatography. The structures of the compounds were identified by physico-chemical properties and spectral analysis. RESULT: Nine compounds were isolated and identified as (+)-maackiain (1), brevifolin (2), 7-hydroxy-4'-methoxy isoflavanone (3), daidzein 4',7-diglucoside (4), genistein 4', 7-di-O-beta-D-glucoside (5), isolupalbigenin (6), ononin (7), beta-sitosterol (8), beta-daucosterol (9). CONCLUSION: Compounds 2, 4 - 6 were obtained from the genus Ammopiptanthus for the first time.