A new isoquinoline and ceramide from the stem barks of Discoglypremna caloneura (Pax) Prain (Euphorbiaceae) with antiproteinase and cytotoxic activities.

Two new compounds, an isoquinoline (1) and caloneuramide (2), a ceramide were isolated from the stem bark of Discoglypremna caloneura together with seven known compounds namely aurantiamide acetate (3), acetylaleuritolic acid (4), 3α-hydroxylaleuritolic acid 2α-p-hydroxybenzoate (5), mixture of stigmasterol (6) and ß-sitosterol (7), mixture of 7-oxo-stigmasterol (8) and 7-oxo-ß-sitosterol (9). Their structures were determined based on data from literature and spectroscopic methods. Derivatization reactions on the isoquinoline led to two new compounds, the methylated (10) and acetylated (11) derivatives. Some compounds and extracts were evaluated for their cytotoxic and antiproteinase activity. Antiproteinase effect of compounds 1, 10 and 11 exhibited IC50 values of 10.77, 1.19 and 3.61 µg/mL respectively; significantly low compared to the standard drug, acetyl salicylic acid (IC50 = 20.28 µg/mL). Ethyl acetate and methanol extract exhibited moderate cytotoxicity activity on Chang liver cells with CC50 values of 167.90 ± 2.20 and 106.30 ± 2.03 µg/mL compared to the reference drug cucurmin (CC50 = 11.05 ± 1.04 µg/mL).

Two new flavones glycosides with antimicrobial activities from Clerodendrum formicarum Gürke (Lamiaceae).

Clerodendrum formicarum Gürke from the Lamiaceae family is a Cameroonian medicinal plant. The crude methanol, methanol residual and ethyl acetate extracts of leaves have been phytochemically studied using chromatography column to afford four compounds; two new flavones glycoside: clerodendronone 1a (3) and clerodendronone 1b (4) along with two known compounds: 5,7-dihydroxy-4'-methoxyflavone (1) and 5-hydroxy-7,4'-dimethoxyflavone (2). Compound structures have been elucidated on the basis of their spectroscopy data and with literature information. The anti-microbial activities of extracts and three isolated compounds were performed. The antibacterial activity was evaluated against four gram positive, five gram negative and three fungus. Clerodendronone 1b (4) showed good antibacterial activity against bacterial gram negative Shigella flexineri NR518 (MIC = 62.5 µg/ml) and moderate activity against Staphylococcus aureus NR46374 (MIC = 250 µ/ml). The ethyl acetate extract recorded good antibacterial activity against Staphylococcus aureus NR46003 (MIC = 125 µg/ml) and Staphylococcus aureus NR46374 (MIC = 125 µg/ml).

Antifungal potential of extracts, fractions and compounds from Uvaria comperei (Annonaceae) and Oxyanthus unilocularis (Rubiaceae).

Phytochemical study of Uvaria comperei afforded an alkaloid, 8,9-dimethoxy-5H-phenanthridin-6-one (1), isolated and characterised (assignment of 1H and 13C NMR) for the first time from a natural source along with two flavonoids, (2S)-5-hydroxy-7,8-dimethoxyflavanone (2) and (2S)-7-hydroxy-5-methoxy-6,8-dimethylflavone (3). Clethric acid (4), oleanoic acid (5), ß-sitosterol 3-O-ß-D-glucopyranoside (9), ß-sitosterol palmitate (6) and a mixture of stigmasterol (7) and ß-sitosterol (8) were isolated from Oxyanthus unilocularis. The structures of these compounds were elucidated using modern spectroscopic techniques including1D and 2D Nuclear Magnetic Resonance (NMR) Spectroscopy (1H, 13C, 1H-1H COSY, HSQC, HMBC) and Mass Spectrometry. Some fractions and compounds from Uvaria comperei exhibited good antifungal activity against clinical isolates and standard strains of yeast species of Candida and Cryptococcus genera while extracts from Oxyanthus unilocularis displayed weak antifungal activity. The results obtained show that Uvaria comperei could be a potential source of antifungal drugs.

Anti-Inflammatory and Analgesic Effect of Arachic Acid Ethyl Ester Isolated from Propolis.

Inflammatory diseases are a real public health problem worldwide. Many synthetic drugs used in the treatment of inflammatory diseases such as steroidal anti-inflammatory drugs, nonsteroidal anti-inflammatory drugs (NSAIDs) and immunosuppressive drugs have harmful side effects. However, there are natural products like propolis, which is traditionally used in the treatment of pain. The objective of this work was to evaluate the anti-inflammatory and analgesic activities of the ethyl ester of arachic acid, a compound isolated from Cameroonian propolis. The ethyl ester of arachic acid was isolated by chromatography of the ethanolic extract of propolis harvested at Tala-Mokolo (Far North Region of Cameroon) and identified by nuclear magnetic resonance (NMR) spectra and the 1H-1H correlated spectroscopy. The anti-inflammatory and analgesic properties of oral administration of arachic acid ethyl ester (12.5, 25.0, and 50.0 mg/kg bw) were evaluated using carrageenan-induced paw edema, xylene-induced ear edema, cotton pellets-induced granuloma formation, and hot plate test in rat. Arachic acid ethyl ester produced maximum inhibition at 50.0 mg/kg for carrageenan-induced paw edema (62.5%), xylene-induced ear edema (54.5%), cotton pellet-induced granuloma (47.4%), and increased mean latency for hot plate test in rats. These results show clearly that the arachic acid ethyl ester has acute and chronic anti-inflammatory properties as well as central analgesic properties. This justifies the use of propolis in the treatment of pain in traditional medicine.

Excelsanone, a new isoflavonoid from Erythrina excelsa (Fabaceae), with in vitro antioxidant and in vitro cytotoxic effects on prostate cancer cells lines.

A new isoflavonoid, excelsanone (2), was isolated from the ethyl acetate extract of Erythrina excelsa stem bark, together with three known compounds namely 6,8-diprenylgenistein (3), ß-sitosterol (1) and sitosteryl-ß-D-glucopyranoside (4). Their structures were elucidated using spectroscopic methods (HR-ESI-MS, NMR and IR) and by comparison with some literature data. The antioxidant activity of crude extracts and two isolated compounds was evaluated using free radical scavenging (DPPH) and Ferric Reducing Ability Power (FRAP) methods with catechin as standard. The results of the radical scavenging activity showed that excelsanone (2) has a moderate potential with an IC50 of 1.31 mg/ml. The cytotoxicity of compounds 2 and 3 as well as the ethyl acetate extract was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in two prostate cancer cell lines (DU145 and PC3). Excelsanone (2) induced a greater cytotoxicity in all tested cell lines, with a significant inhibition of DU145 cells growth in a concentration-dependent manner.

Cordidepsine is A Potential New Anti-HIV Depsidone from Cordia millenii, Baker.

Chemical investigation of Cordia millenii, Baker resulted in the isolation of a new depsidone, cordidepsine (1), along with twelve known compounds including cyclooctasulfur (2), lup-20(29)-en-3-triacontanoate (3), 1-(26-hydroxyhexacosanoyl)glycerol (4), glyceryl-1-hexacosanoate (5) betulinic acid (6), lupenone (7), ß-amyrone (8), lupeol (9), ß-amyrin (10), allantoin (11), 2'-(4-hydroxyphenyl)ethylpropanoate (12) and stigmasterol glycoside (13). Hemi-synthetic reactions were carried out on two isolated compounds (5 and 6) to afford two new derivatives, that is, cordicerol A (14) and cordicerol B (15), respectively. The chemical structures of all the compounds were established based on analysis and interpretation of spectroscopic data such as electron ionization mass spectrometry (EI-MS), high resolution electrospray ionization mass spectrometry (HR-ESI-MS), fast atom bombardment mass spectrometry (FAB-MS), one dimension and two dimension nuclear magnetic resonance (1D and 2D-NMR) spectral data as well as X-ray crystallography (XRC). Lupeol ester derivatives [Lup-20(29)-en-3-triacontanoate (3)], monoglycerol derivatives [1-(26-hydroxyhexacosanoyl)glycerol (4) and glyceryl-1 hexacosanoate (5)] were isolated for the first time from Cordia genus while sulfur allotrope [cyclooctasulfur (2)] was isolated for the first time from plant origin. Biological assays cordidepsine (1) exhibited significant anti-HIV integrase activity with IC50 = 4.65 µM; EtOAc extract of stem barks, EtOAc fraction of roots and leaves were not toxic against 3T3 cells.

New prenylated isoflavonoids as protein tyrosine phosphatase 1B (PTP1B) inhibitors from Erythrina addisoniae.

Bioassay-guided fractionation of the EtOAc extract of the root of Erythrina addisoniae (Leguminosae) resulted in the isolation of four new (1-4), along with 2 known prenylated isoflavonoids (5-6). The structures of the isolates were assigned on the basis of spectroscopic data analysis, focusing on interpretation of 1D and 2D NMR, and MS data. All the isolates were evaluated for their inhibitory effects on protein tyrosine phosphatase 1B (PTP1B), as well as their growth inhibition on MCF7, adriamycin-resistant MCF7 (MCF7/ADR), and MDA-MB-231 breast cancer cell lines. Compounds which exhibited PTP1B inhibitory activity (IC(50) values ranging from 4.6 ± 0.3 to 24.2 ± 2.1 µM) showed potential cytotoxic activity (IC(50) values ranging from 3.97 ± 0.17 to 11.4 ± 1.9 µM). Taken together, our data suggest that prenylated isoflavonoids, especially the isoflavone-type skeleton could be considered as new lead compounds against breast cancer via PTP1B inhibition.

Evaluation of the sedative and anticonvulsant properties of three Cameroonian plants.

Millettia thonningii, Ocinum sanctum and Securitaca longepedunculaca are used in traditional medicine in Cameroon to treat epilepsy, insomnia and headaches. Animal models of epilepsy (maximal electroshock (MES), n-methyl-d-aspartate (NMDA), pentylenetetrazol (PTZ), isonicotinic hydrazide acid (INH), picrotoxine (PIC) and strychnine (STR)-induced convulsions or turning behavior were used to evaluate anticonvulsant activity while diazepam-induced sleep test was used to evaluate sedative activity of the plants. Four doses of extracts were used for each plant (100, 200, 500 and 1000 mg/kg). At a dose of 1000 mg/kg, Millettia thonningii protected 60 and 90% of mice against MES and PTZ-induced convulsions, respectively. At the same dose, Millettia thonningii also protected 80% of mice against NMDA-induced turning behavior. At a dose of 1000 mg/kg, Ocinum sanctum provided complete protection against MES, PIC and STR- induced convulsions and 83.3% of protection in PTZ test. Securitaca longepedunculata completely protected (100%) mice in PIC test at a dose of 200 mg/kg, in MES test at a dose of 500 mg/kg and in PTZ test at a dose of 1000 mg/kg. 66.7% of mice were protected against STR-induced convulsions. All the three plants showed also sedative properties for they increased significantly and in a dose dependent manner the total sleep time induced by diazepam. The total sleep time of the control groups was multiplied by a factor of 3 at least by each extract. The presence of sedative and anticonvulsant activity in the three plants could explain their use in traditional medicine in the treatment of epilepsy and insomnia in Cameroon.

New prenylated flavanones from Erythrina abyssinica with protein tyrosine phosphatase 1B (PTP1B) inhibitory activity.

As the insulin and leptin signaling pathway can be regulated by PTP1B, it has been suggested that compounds that reduce PTP1B activity or expression levels can be used for treating type 2 diabetes and obesity. In the course of our screening efforts on new PTP1B inhibitors, six new flavanones ( 1- 6) with dihydrofuran moiety and two known flavanones ( 7 and 8) were isolated from the stem bark of Erythrina abyssinica (Leguminosae). Their structures were elucidated on the basis of spectroscopic (including UV, CD, MS, 1D, and 2D NMR) and physicochemical analyses. With the exception of 3 and 5, the compounds inhibited PTP1B activity in an IN VITRO assay with IC (50) values ranging from 15.2 +/- 1.2 to 19.6 +/- 2.3 microM, whereas RK-682 as a positive control displayed an IC (50) value of 4.7 +/- 0.5 microM.

Vasorelaxant effects of extracts of the stem bark of Terminalia superba Engler & Diels (Combretaceae).

AIM OF THE STUDY: The stem bark of Terminalia superba (Combretaceae) (TS) is used in traditional Cameroonian medicine as antihypertensive remedy. In the present study, we investigated the vasorelaxant properties of different extracts of TS and their underlying mechanisms. MATERIALS AND METHODS: Activities of aqueous (AQU), methanolic (MET), methylene chloride (MC), and methylene chloride-methanol (MCM) extracts of TS were evaluated on isolated rat aortic rings precontracted with phenylephrine (PE) or high KCl. RESULTS: All extracts induced a vasodilating effect both on KCl- and PE-induced contractions. The effects of MC and MCM extracts were greater than those of AQU or MET extracts (P<0.05). MC had an endothelium-independent effect and reduced Ca(++)-induced contraction following PE or KCl challenge (P<0.05). After incubation with verapamil, MC induced a relaxation in rings precontracted by PE (P<0.001). By contrast, the effect of MCM was endothelium-dependent and decreased by the nitric oxide synthase inhibitor N(W)-nitro-L-arginine methyl ester (P<0.05). CONCLUSIONS: These data demonstrate that the MC extract exhibits vasorelaxant effects that are partly due to inhibition of extracellular Ca(++) influx and/or inhibition of intracellular Ca(++) release in vascular smooth muscle cells. By contrast, the effect of the MCM extract was found to be endothelium- and nitric oxide dependent.

Pterocarpans with inhibitory effects on protein tyrosine phosphatase 1B from Erythrina lysistemon Hutch.

Bioassay-guided fractionation of the MeOH extract of the stem bark of Erythrina lysistemon Hutch. resulted in isolation of pterocarpans (1-3), named erylysins A-C, along with nine known pterocarpans (4-12). Their structures were determined to be 3''-hydroxy-2',2'-dimethylpyrano[6',5':3,4]-2'',2''-dimethyldihydropyrano[6'',5'':9,10]pterocarpan (1), furano[5',4':3,4]-9-hydroxy-10-prenylpterocarpan (2), and 8-formyl-3,9-dihydroxy-4,10-diprenylpterocarpan (3), based on spectroscopic analyses. All the isolates, with the exception of 3, 6, and 11, strongly inhibited protein tyrosine phosphatase 1B (PTP1B) activity in an in vitro assay, with IC(50) values ranging from 1.01+/-0.3 to 18.1+/-0.9 microg/mL. This is the first report showing the potential of prenylated pterocarpans as a class of natural PTP1B inhibitors.

Hypoglycaemic and antihyperglycaemic activity of Ageratum conyzoides L. in rats.

The hypoglycaemic and antihyperglycaemic properties of the aqueous extracts of the leaves of Ageratum conyzoides L. were evaluated in normoglycemic and in streptozotocin-induced diabetic rats, in order to validate its use in folk medicine. Tested animals were given the aqueous extracts of the plant at the doses of 100, 200 and 300mg/kg. These doses were tested also on glucose loaded normal male rats (Oral Glucose Tolerance Test). Of all the doses, the aqueous extracts at 200 and 300mg/kg showed statistically significant hypoglycaemic and antihyperglycaemic activities. For the oral glucose tolerance test, 100mg/kg dose only attenuated significantly the rise of blood glucose in normal fasted rats. Consequently, these results confirmed the hypoglycaemic properties of the leaves of Ageratum conyzoides.

Flavanones from the stem bark of Erythrina abyssinica.

Twelve new flavanones bearing a 2,2-dimethylpyrano ring were isolated from a MeOH extract of the stem bark of Erythrina abyssinica. Their structures were determined on the basis of spectroscopic (UV, CD, 1D and 2D NMR, HRMS) and physico-chemical analyses. Compounds 1, 3, 5, 6, 8, and 9 exhibited inhibitory effects on the enzyme activity of PTP1B in an in vitro assay with IC(50) values ranging from 13.9+/-2.1 to 19.0+/-1.8 microM. These results suggest that prenyl and methoxy groups on the B ring contribute to the inhibitory activity of flavanones against PTP1B.

Four new chalcones from Erythrina abyssinica.

Four new chalcones 1 - 4, named abyssinones A - D, were isolated from the stem bark of the plant Erythrina abyssinica and their structures were elucidated on the basis of spectroscopic analyses. The compounds 1, 3, and 4 were found to exhibit moderate cytotoxic activity against the human colorectal cancer cell line (Caco2) with IC (50) values of 13.3, 15.1, and 11.1 microM, respectively.

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.

Isoprenylated flavonoids from the stem bark of Erythrina abyssinica.

Three new prenylated flavanones, abyssinoflavanones V, VI, and VII (1-3), together with eight known flavanones (4-11) and two chalcones (12-13), were isolated from the stem bark of Erythrina abyssinica. Their structures were elucidated on the basis of spectroscopic and physicochemical analyses. All the isolates, with the exception of 1 and 8, strongly inhibited PTP1B activity in an in vitro assay with IC50 values ranging from 14.2 +/- 1.7 to 26.7 +/- 1.2 microM.

Protein tyrosine phosphatase-1B inhibitory activity of isoprenylated flavonoids isolated from Erythrina mildbraedii.

Inhibition of protein tyrosine phosphatase-1B (PTP1B) has been proposed as a therapy for treatment of type-2 diabetes and obesity. Bioassay-guided fractionation of an EtOAc-soluble extract of the root bark of Erythrina mildbraedii, using an in vitro PTP1B inhibitory assay, resulted in the isolation of three new isoprenylated flavonoids, abyssinone-IV-4'-O-methyl ether (2), 7-hydroxy-4'-methoxy-3'-(3-hydroxy-3-methyl-trans-but-1-enyl)-5'-(3-methylbut-2-enyl)flavanone (3), and abyssinone-VI-4-O-methyl ether (6), along with six known flavonoids, abyssinone-V-4'-O-methyl ether (1), abyssinone-V (4), abyssinone-IV (5), sigmoidin E (7), 4'-hydroxy-5,7-dimethoxyisoflavone (8), and alpinumisoflavone (9). Compounds 1 and 2, 4-7, and 9 inhibited PTP1B activity, with IC50 values ranging from 14.8 +/- 1.1 to 39.7 +/- 2.5 microM. On the basis of the data obtained, flavanones and chalcones with isoprenyl groups may be considered as a new class of PTP1B inhibitors.

Inhibition of protein tyrosine phosphatase 1B by prenylated isoflavonoids isolated from the stem bark of Erythrina addisoniae.

It has been suggested that protein tyrosine phosphatase 1B (PTP1B) inhibitors might be a therapeutic target for the treatment of type 2 diabetes and obesity. A bioassay-guided phytochemical study of the EtOAc extract of the stem bark of Erythrina addisoniae (Leguminosae) resulted in the identification of a new PTP1B inhibitory compound, 5,2',4'-trihydroxy-6-(gamma,gamma-dimethylallyl)-2''',2'''-dimethyldihydropyrano[5''',6''']isoflavanone ( 6), along with five known prenylated isoflavonoids, orientanol E ( 1), senegalensin ( 2), warangalone ( 3), warangalone 4'-methyl ether ( 4) and 2,3-dihydroauriculatin ( 5). Compounds 1, 5 and 6 inhibited PTP1B with IC (50) values ranging from 2.6 +/- 0.5 to 10.1 +/- 0.3 microM. Our results indicate that hydroxylation at both 2'- and 4'-positions in the B-ring and cyclization between a hydroxy group at C-7 and one of the prenyl groups at C-6 or C-8 in the A-ring may be important for activity. Thus, compounds 5 and 6 could be a new class of natural PTP1B inhibitors.

Two biflavonoids from Ouratea nigroviolacea.

The leaves of Ouratea nigroviolacea (Ochnaceae) afforded two biflavonoids, ouratine A and B together with agathisflavone and stigmasterol. The biflavonoids were characterized as 4'-O-methylated apigeninyl-(I-6, II-8)-4'-O-methylatedapigenin and 4'-O-methylated apigeninyl-(I-6, II-8) apigenin by spectral and chemical transformation studies.

Anti-inflammatory activities of two flavanones, sigmoidin A and sigmoidin B, from Erythrina sigmoidea.

Two prenylated flavanones isolated from Erythrina sigmoidea Hua (sigmoidin A and sigmoidin B) were studied for their ability to inhibit the stable 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical and arachidonic acid metabolism. In addition, the compounds were studied in two experimental models of inflammation induced in mouse ears by 12- O-tetradecanoylphorbol 13-acetate (TPA) and the phospholipase A (2)-induced mouse paw oedema. Both sigmoidins A and B proved to be potent scavengers of the DPPH radical, while the study of the inhibition of arachidonic acid metabolism demonstrated that these same compounds were selective inhibitors of 5-lipoxygenase, with no effect on cyclooxygenase-1 activity. Dose-response inhibitor potency was established for sigmoidin A (IC (50) = 31 microM). In the assay of phospholipase A (2)-induced mouse paw oedema, only the sigmoidin B derivative inhibited oedema formation at 60 min, showing a percentage of inhibition below that obtained with cyproheptadine (59 % vs. 74 %). In the TPA test, sigmoidins A and B decreased the induced oedema by 89 % and 83 %, respectively. This is the first time that the anti-inflammatory activity and antioxidant properties of these prenylflavanones have been reported. The results indicate that the compounds have different mechanisms of action depending on whether one or two prenyl groups are present in ring B.