RESUMO
Antrocaryon klaineanum is traditionally used for the treatment of back pain, malaria, female sterility, chlamydiae infections, liver diseases, wounds, and hemorrhoid. This work aimed at investigating the bioactive compounds with antileishmanial and antiplasmodial activities from A. klaineanum. An unreported glucocerebroside antroklaicerebroside (1) together with five known compounds (2-6) were isolated from the root barks of Antrocaryon klaineanum using chromatographic techniques. The NMR, MS, and IR spectroscopic data in association with previous literature were used for the characterization of all the isolated compounds. Compounds 1-4 are reported for the first time from A. klaineanum. The methanol crude extract (AK-MeOH), the n-hexane fraction (AK-Hex), the dichloromethane fraction (AK-DCM), the ethyl acetate fraction (AK-EtOAc), and compounds 1-6 were all evaluated for their antiparasitic effects against Plasmodium falciparum strains susceptible to chloroquine (3D7), resistant to chloroquine (Dd2), and promastigotes of Leishmania donovani (MHOM/SD/62/1S). The AK-Hex, AK-EtOAc, AK-MeOH, and compound 2 were strongly active against Dd2 strain with IC50 ranging from 2.78 ± 0.06 to 9.30 ± 0.29 µg/mL. Particularly, AK-MeOH was the most active-more than the reference drugs used-with an IC50 of 2.78 ± 0.06 µg/mL. The AK-EtOAc as well as all the tested compounds showed strong antileishmanial activities with IC50 ranging from 4.80 ± 0.13 to 9.14 ± 0.96 µg/mL.
Assuntos
Anacardiaceae , Antimaláricos , Antiprotozoários , Antimaláricos/farmacologia , Antimaláricos/química , Anacardiaceae/química , Extratos Vegetais/química , Antiprotozoários/farmacologia , Cloroquina , Plasmodium falciparumRESUMO
The present research evaluated the antidiabetic and antioxidant properties of M. lucida stem bark (50 and 500mg/kg) and glibenclamide (25mg/kg, standard drug) in acute (Oral glucose tolerance test) and sub-acute (Streptozotocin 60mg/kg, i.p. diabetic model) administration. A group of healthy rats constituted the normal control. The sub-acute experiment lasted 28 days during which water, food intake and weight gain were measured and biochemical parameters analyzed in both plasma and erythrocytes at the end of the experiment. The chemical substances present in M. lucida bark extract were determined. In the Oral glucose tolerance test, the reduction of blood glucose level was statistically significant for both M. lucida extracts and glibenclamide. However, in the diabetic rats acute administration of 500mg/kg extract had better blood sugar lowering effect than glibenclamide, which was better than 50mg/kg extract. Streptozotocin diabetic animal model was characterized by a decrease in weight gain, erythrocyte SOD and CAT activities and an increase in water and food consumption, lipid peroxidation, cholesterol, triglycerides, plasma glucose, creatinine and urea concentrations, and transaminases activities. M. lucida extract and glibenclamide significantly prevented the alteration of these parameters, thus indicating a corrective effect on diabetes and its complications. This study justifies the traditional claim and provides a rationale for the use of M. lucida to treat diabetes. Its antioxidant properties may serve to curb oxidative stress and hence prevent the diabetic complications related to oxidative stress. Chemical substances, which may be accountable for the antidiabetic and antioxidant properties of M. lucida were detected in the aqueous extract of M. lucida bark.
Assuntos
Antioxidantes/farmacologia , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/farmacologia , Morinda/química , Extratos Vegetais/farmacologia , Estreptozocina , Animais , Antioxidantes/isolamento & purificação , Biomarcadores/sangue , Glicemia/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Teste de Tolerância a Glucose , Glibureto/farmacologia , Hipoglicemiantes/isolamento & purificação , Peroxidação de Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Casca de Planta , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Ratos , Fatores de TempoRESUMO
A recently developed NMR method to simultaneously obtain both long-range heteronuclear correlations and carbon multiplicity information in a single experiment, ME-selHSQMBC, is demonstrated as a potentially useful technique for chemical shift assignment and structure elucidation of natural products presenting complicated NMR spectra. Carbon multiplicities, even for C/CH2 and odd for CH/CH3 resonances, can be distinguished directly from the relative positive/negative phase of cross-peaks. In addition, connectivity networks can be further extended by incorporating a TOCSY propagation step. Staurosporine (1) and sungucine (2) are utilized as model compounds to demonstrate these techniques.
Assuntos
Produtos Biológicos/química , Carbono/química , Ressonância Magnética Nuclear Biomolecular/métodos , Estrutura Molecular , Estaurosporina/química , Estricnina/químicaRESUMO
A reinvestigation of the roots of Strychnos icaja resulted in the isolation of a new bisindole alkaloid named strychnobaillonine (1) with original C-17-N-1' and C-23-C-17' junctions, in addition to sungucine, bisnordihydrotoxiferine, and strychnohexamine (2). Compound 1 showed potent activity against the chloroquine-sensitive 3D7 strain of Plasmodium falciparum in vitro with an IC50 value of 1.1 µM. The structures of the compounds were defined by detailed spectroscopic analyses, especially 1H and 13C NMR, DEPT, HSQC, COSY, NOESY, HMBC, and HRESIMS. The proposed absolute configuration was based on biosynthetic considerations and spectroscopic data (CD, NMR) supported by molecular modeling.
Assuntos
Antimaláricos/química , Antimaláricos/isolamento & purificação , Alcaloides Indólicos/química , Alcaloides Indólicos/isolamento & purificação , Strychnos/química , Antimaláricos/farmacologia , Camarões , Carbazóis/química , Carbazóis/isolamento & purificação , Cloroquina/farmacologia , Alcaloides Indólicos/farmacologia , Concentração Inibidora 50 , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Raízes de Plantas/química , Plasmodium falciparum/efeitos dos fármacos , Estricnina/análogos & derivados , Estricnina/química , Estricnina/isolamento & purificação , Toxiferina/análogos & derivados , Toxiferina/química , Toxiferina/isolamento & purificaçãoRESUMO
From the stem bark of Strychnos malacoclados, one new bisindole alkaloid, 3-hydroxylongicaudatine Y (1), was isolated along with the known alkaloids vomicine (2), bisnordihydrotoxiferine (3), divarine (4), longicaudatine (5), longicaudatine Y (6), and longicaudatine F (7). All the compounds were tested for their antimalarial activity against the chloroquine-sensitive 3D7 and -resistant W2 strains of Plasmodium falciparum. Longicaudatine was the most active compound with IC50 values of 0.682 and 0.573 µM, respectively. The activity of compounds 1, 3, 4, 6, and 7 against the two strains ranged from 1.191 to 6.220 µM and 0.573 to 21.848 µM, respectively. Vomicine (2), the only monomer isolated, was inactive. The alkaloids of the longicaudatine-type ( 1, 5-7) were more active than those of the caracurine-type (3- 4). The presence of the ether bridge in the molecule seems to increase the antiplasmodial activity. Compounds 1, 5, and 7 were tested against the WI-38 human fibroblast cell line. Longicaudatine was the most cytotoxic compound with an IC50 of 2.721 µM. Longicaudatine F was 40-46 times more active against the two strains of P. falciparum than against the human fibroblasts and was thus considered as the more selective alkaloid. The structures of the compounds were determined based on the analysis of their spectral data.
Assuntos
Alcaloides/farmacologia , Antiprotozoários/farmacologia , Strychnos/química , Camarões , Linhagem Celular , Fibroblastos/efeitos dos fármacos , Humanos , Malária Falciparum/tratamento farmacológico , Malária Falciparum/microbiologia , Fitoterapia , Casca de Planta/química , Extratos Vegetais/farmacologia , Caules de Planta/química , Plasmodium falciparum/efeitos dos fármacosRESUMO
Bioassay-guided fractionation of the CH2Cl2-MeOH (1:1) leaves extract of Trichilia gilgiana, yielded two new vilasinin-type limonoids named gilgianin A (1) and gilgianin B (2), one new phenyl alkene derivative designated as gilgialkene A (3), along with six known compounds: rubescin H (4), TS3 (5), trichirubine A (6), sitosteryl-6'-O-undecanoate-ß-D-glucoside (7), scopoletin (8), and octadecane-2-one (9). Their structures were elucidated based on spectroscopic analysis and comparison with literature data. Compounds 5 and 6 exhibited the highest antiplasmodial activity with IC50 values of 1.14 and 1.32 µM respectively. Moreover, compound 5 was very cytotoxic with CC50 value of 0.88 µM, compared to compound 6, which was not cytotoxic (CC50 > 10 µg/mL). Compounds 1 (IC50 = 9.84 µM), 2 (IC50 = 11.04 µM) and 4 (IC50 = 10.71 µM) presented good antiplasmodial activity while also exhibiting significant cytotoxicity, with CC50 values ranging from of 14.45 to 29.7 µM.[Formula: see text].
Assuntos
Antimaláricos , Limoninas , Meliaceae , Alcenos , Antimaláricos/química , Antimaláricos/farmacologia , Bioensaio , Glucosídeos , Limoninas/química , Limoninas/farmacologia , Meliaceae/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Plasmodium falciparum , EscopoletinaRESUMO
One new limonoid, trigilgianin (1), one new phenyl alkene, epoxy gilgialkene (2), together with five known compounds: scopoletin (3), sitosteryl-6'-O-undecanoate-ß-D-glucoside (4), sitosteryl-O-ß-D-glucopyranoside (5), cinchonain A (6) and cinchonain B (7) were isolated from the stem bark of Trichilia gilgiana Harms. (Meliaceae). All compounds were isolated for the first time from this species. The structures were elucidated on the basis of spectral studies and by comparison of these data with those from the literature. Compounds 1, 2, 3, 6 and 7 were tested for in vitro antileishmanial activity against visceral leishmaniasis parasite Leishmania donovani and cytotoxicity against macrophage RAW 264.7 cell line. Compounds 1 and 3 showed the highest antileishmanial activity (IC50 values of 6.044 and 6.804 µg/mL, respectively) with low cytotoxicity (CC50 values of >200 and 47.47 µg/mL, respectively), while compound 2 was moderately active on L. donovani promastigotes (IC50 56.81 µg/mL).
Assuntos
Meliaceae/química , Tripanossomicidas/química , Tripanossomicidas/farmacologia , Alcenos/química , Animais , Leishmania donovani/efeitos dos fármacos , Limoninas/química , Espectroscopia de Ressonância Magnética , Camundongos , Estrutura Molecular , Casca de Planta/química , Células RAW 264.7 , Escopoletina/isolamento & purificaçãoRESUMO
Three prenylated rotenoids, elliptol, 12-deoxo-12alpha-methoxyelliptone and 6-methoxy-6a,12a-dehydrodeguelin were isolated from the twigs of Millettia duchesnei, together with the known compounds, 6a,12a-dehydrodeguelin, 6-hydroxy-6a,12a-dehydrodeguelin, 6-oxo-6a,12a-dehydrodeguelin, elliptone, 12a-hydroxyelliptone and eriodictyol. Their structures were elucidated on the basis of spectral data and comparison with information reported in the literature and with authentic specimens for some known compounds. The full NMR data of 6-oxo-6a,12a-dehydrodeguelin and 6-hydroxy-6a,12a-dehydrodeguelin are reported here for the first time.
Assuntos
Millettia/química , Componentes Aéreos da Planta/química , Rotenona/análogos & derivados , Rotenona/isolamento & purificação , Espectroscopia de Ressonância Magnética , Rotenona/químicaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Decoctions of the leaves of M. benthamianum Baill. are used by traditional healers in Guinea to treat malaria and this use was validated by a preliminary clinical assay. AIM OF THE STUDY: To evaluate the in vitro antiplasmodial activity and to identify active compounds from extracts of M. benthamianum leaves. MATERIAL AND METHODS: Antiplasmodial activity of extracts, fractions and pure compounds was evaluated in vitro against a chloroquine-sensitive strain of Plasmodium falciparum (3D7) using the measurement of the plasmodial lactate dehydrogenase activity. Selectivity of extracts and purified compounds for Plasmodium parasites was evaluated by using WST-1 test on HeLa human cells. Compounds were isolated using normal phase silica gel column chromatography and prepHPLC and their structures elucidated using extensive spectroscopic analysis. RESULTS: Hydroethanolic extracts (70% v/v) of M. benthamianum leaves showed a moderate in vitro activity against P. falciparum 3D7, with IC50 in the range 22.5 - 32.6µg/mL, depending on the batch; while a dark precipitate formed during ethanol evaporation showed higher activity (IC50 =6.5µg/mL). The fractionation was performed on this most active fraction and was followed by in vitro antiplasmodial assay. Active compounds (5, 7, 8) belong to several phytochemical classes, contributing together to the global antiplasmodial activity of the hydroethanolic extract against P. falciparum parasite. This study finally allowed the isolation of three diterpenes including two new compounds named Mezobenthamic acids A (1) and B (2) and neocaesalpin H (3), as well as quercetin (4), kaempferol (7), resveratrol (6), gallic acid (9) and its ethylester (5), ß-sitosterol glucoside (10) and 13b-hydroxy-pheophorbide a (8). CONCLUSION: This study gives some concrete evidence to support the ethnopharmacological use of Mezoneuron benthamianum leaves extract in the management of malaria. The active compounds can be further studied for their antiplasmodial potential, as well as their suitability to be used as quality markers for the standardization of this herbal drug from the Guinean traditional pharmacopeia.
Assuntos
Antimaláricos/farmacologia , Caesalpinia/química , Extratos Vegetais/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Antimaláricos/química , Antimaláricos/isolamento & purificação , Cloroquina/farmacologia , Cromatografia Líquida de Alta Pressão , Etnofarmacologia , Guiné , Células HeLa , Humanos , Concentração Inibidora 50 , Medicina Tradicional , Testes de Sensibilidade Parasitária , Extratos Vegetais/química , Folhas de Planta , Análise EspectralRESUMO
BACKGROUND: Entada abyssinica is a plant traditionally used against gastrointestinal bacterial infections. Eight compounds including three flavonoids, three terpenoids, a monoglyceride and a phenolic compound isolated from E. abyssinica were investigated for their cytotoxicity, antibacterial and antioxidant activity. RESULTS: Compounds 7 and 2 had remarkable activity against Salmonella typhimurium with the lowest respective minimum inhibitory concentration (MIC) values of 1.56 and 3.12 µg/mL. The antioxidant assay gave IC50 values varied from 0.48 to 2.87 µg/mL in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, from 2.53 to 17.04 µg/mL in the 2,2'-Azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt (ABTS) assay and from 1.43 to 103.98 µg/mL in the FRAP assay. Compounds had relatively low cytotoxicity (LC50 values ranging from 22.42 to 80.55 µg/mL) towards Vero cells. Ursolic acid had the most potent cytotoxicity against THP-1 and RAW 264.7 cells with LC50 values of 9.62 and 4.56 µg/mL respectively, and selectivity index values of 7.32 and 15.44 respectively. CONCLUSION: Our findings suggest that among the terpenoid and flavonoid compounds studied, entadanin (compound 7) possess tremendous antibacterial activity against S. typhimurium and could be developed for the treatment of bacterial diseases.
Assuntos
Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Citotoxinas/farmacologia , Fabaceae , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Extratos Vegetais/farmacologia , Plantas Medicinais , África , Anti-Infecciosos/isolamento & purificação , Antioxidantes/isolamento & purificação , Bacillus cereus/efeitos dos fármacos , Citotoxinas/isolamento & purificação , Enterococcus faecalis/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Casca de Planta , Extratos Vegetais/isolamento & purificação , Folhas de Planta , Caules de Planta , Pseudomonas aeruginosa/efeitos dos fármacos , Salmonella typhimurium/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacosRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Heinsia crinita is used in traditional medicine for the treatment of febrile illness and erectile dysfunction. Its stem bark powder is found in some peripheral markets in the Democratic Republic of the Congo (DRC) as a remedy against malaria. Investigations were conducted on crude extracts of leaves, fruits and stem barks in view to validate their use and to determine which plant part possesses the best antiplasmodial properties. MATERIALS AND METHODS: Different plant parts were extracted with methanol, ethanol and dichloromethane. Based on the preliminary assays, the dichloromethane extract of the stem bark was subjected to fractionation using preparative HPLC system and column chromatography. This step led to the isolation of two new iridoids which had their structures elucidated by NMR, UV, MS and FT-IR spectroscopic techniques. Extracts and pure compounds were tested in vitro against the 3D7 strain of Plasmodium falciparum. The inhibition of the parasite growth was evaluated in vitro by colorimetric method (p-LDH assay) and their cytotoxicity evaluated in vitro against the human non-cancer fibroblast cell line (WI38) through WST1 assay. The in vivo antiplasmodial activity was assessed by the inhibition of Plasmodium berghei growth in infected mice treated with the ethanol extract of H. crinita stem bark at the concentrations of 200 and 300mg/Kg/day per os, using a protocol based on the 4-d suppressive test of Peters and compared to a non-treated negative control group of mice (growth =100%). Finally the antioxidant activity of the same extract was evaluated using ABTS, DPPH and cell-based assays. RESULTS: A moderate in vitro antiplasmodial activity was observed for the dichloromethane extract of the stem bark of H. crinita (IC50 =29.2±1.39µg/mL) and for the two new iridoids, lamalbide 6, 7, 8- triacetate (IC50 =16.39±0.43µg/mL) as well as for its aglycone lamiridosin 6, 7, 8-triacetate (IC50 =0.44.56±1.12µg/mL). The ethanolic stem bark extract (200 and 300mg/kg/day, oral route) showed a moderate in vivo antimalarial activity in Plasmodium berghei-infected mice with 27.84±2.75% and 48.54±3.76% of inhibition of the parasite growth, respectively (p<0.01).). This extract displayed high cellular antioxidant activity using dichlorofluorescein-diacetate (DCFDA) on HL-60 monocytes. These crude extracts and pure compounds tested at the higher concentration of 100µg/mL did not show any cytotoxicity against WI38 cells. CONCLUSIONS: The results showed that H. crinita extracts possess antimalarial activity and contain some unusual iridoids with moderate antiplasmodial activity, therefore justifying to some extent its traditional use by the local population in DRC for this purpose. This is the first report of the isolation and antiplasmodial activity of these two new iridoids.
Assuntos
Antimaláricos , Iridoides , Malária/tratamento farmacológico , Extratos Vegetais , Rubiaceae , Animais , Antimaláricos/análise , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Feminino , Frutas , Células HL-60 , Humanos , Iridoides/análise , Iridoides/farmacologia , Iridoides/uso terapêutico , Malária/parasitologia , Camundongos , Casca de Planta , Extratos Vegetais/análise , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Folhas de Planta , Plasmodium berghei/efeitos dos fármacos , Plasmodium berghei/crescimento & desenvolvimento , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/crescimento & desenvolvimento , Espécies Reativas de Oxigênio/metabolismoRESUMO
A new dihydroflavonol-flavonol biflavonoid derivative, named ericoside was isolated from the ethanol extract of the whole plant of Erica mannii along with the known flavonoid, taxifolin 3-O-α-L-rhamnopyranoside; and two readily available sterols (sitosterol, sitosterol 3-O-ß-D-glucopyranoside). The isolation was performed using chromatographic methods and the structure of purified molecules were elucidated using spectroscopic techniques (e.g. MS, NMR) and by comparison with literature data. The crude ethanol extract, ericoside, and taxifolin 3-O-α-L-rhamnopyranoside were tested against ten Gram-negative bacteria including multidrug resistant clinical isolates using a broth microdilution method. The crude ethanol extract showed no noteworthy activity. Of the purified compounds, ericoside displayed moderate activity against the resistant Escherichia coli AG100 with a MIC of 64 µg/mL.
Assuntos
Antibacterianos/química , Biflavonoides/química , Ericaceae/química , Antibacterianos/isolamento & purificação , Biflavonoides/isolamento & purificação , Camarões , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Extratos Vegetais/químicaRESUMO
A phytochemical investigation of the whole plant of Crassocephalum bauchiense Huch. resulted in the isolation of a new clerodane diterpenoid, ent-2ß,18,19-trihydroxycleroda-3,13-dien-16,15-olide (1), together with two known flavonoids 3',5-dihydroxy-4',5',6,7,8-pentamethoxyflavone (2) and 4',5-dihydroxy-3',5',6,7,8-pentamethoxyflavone (3). The compounds were tested against the chloroquine-sensitive 3D7 strain of Plasmodium falciparum. Compound 2 showed weak activity (IC50 = 10.1 g/mL) whilst compounds 1 and 3 were inactive. The structures of the compounds were elucidated by using detailed spectral analyses, especially (1)H and (13)C NMR, (1)H-(1)H COSY, NOESY, HMBC and HR-ESI-MS.
Assuntos
Antimaláricos/química , Asteraceae/química , Diterpenos Clerodânicos/química , Plasmodium falciparum/efeitos dos fármacos , Antimaláricos/isolamento & purificação , Diterpenos Clerodânicos/isolamento & purificação , Concentração Inibidora 50 , Estrutura Molecular , Extratos Vegetais/químicaRESUMO
A majority of Africans rely on traditional medicine as the primary form of health care. Yet most traditional medicine products have a short shelf life, especially for water-based formulations such as macerations, infusions and decoctions. Indeed, many of these water extracts become unfit for human consumption after five to seven days of conservation either because of the degradation or toxicity of active components, and/or the growth of pathogenic organisms. The purpose of this study was to describe and apply a new approach for the development of an improved traditional medicine (ITM) that is cheap, very efficient, not toxic, and easy to produce, and that can be conserved for a longer time without a significant loss of activity. Hence, Laportea ovalifolia was selected from an ethnobotanical prospection in all regions of Cameroon, and was used to prepare an oral hypoglycemic product. This preparation required 9 steps focused on the characterization of the plant species, and the standardization of the ethnopharmacological preparation by a multidisciplinary team of scientists with expertise in botany, ecology, pharmacognosy and pharmacology. Resultantly, four galenic formulations of hypoglycemic medications were produced. A relationship between these four formulations was described as follow: One spoon of oral suspension (10 ml)=one sachet of powder=2 tablets=3 capsules. Hence, our research provides new insight into a drug discovery approach that could alleviate the major problems affecting traditional medicine and enhance its effectiveness in addressing health care in developing and undeveloped countries.
RESUMO
During a study on the chemistry and biological activity of Antrocaryon klaineanum Pierre, six new sterols including 4,24(28)-ergostadiene-6α,7α-diol (1), 6α-methoxy-4,24(28)-ergostadiene-7α,20S-diol (2), 6α-methoxy-4,24(28)-ergostadien-7α-ol (3), 20S-hydroxy-24(28)-ergosten-3-one (4), 7α-hydroxy-4,24(28)-ergostadien-3-one (5), and 24(28)-ergostene-3ß,6α-diol (6) were characterized by physical and spectroscopic means. The known steroids 7 and 8 were also isolated. The crude extract and the isolated compounds were evaluated for their ability to inhibit the 3D7 strain of Plasmodium falciparum. Compounds 2, 3, and 8 showed potent activity while that of the crude extract was moderate.
Assuntos
Anacardiaceae/química , Antimaláricos/química , Antimaláricos/farmacologia , Esteroides/farmacologia , Avaliação Pré-Clínica de Medicamentos/métodos , Ergosterol/análogos & derivados , Ergosterol/química , Ergosterol/isolamento & purificação , Ergosterol/farmacologia , Concentração Inibidora 50 , Estrutura Molecular , Casca de Planta/química , Extratos Vegetais/análise , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Esteroides/químicaRESUMO
Vernoguinoside, 16beta,22R;21,23S-diepoxy-3beta-O-beta-D-glucopyranosyloxy-21S,24-dihydroxy-5alpha-stigmasta-8,14-dien-28-one (1), a new stigmastane derivative, 16beta,22R;21,23S-diepoxy-21S,24-dihydroxy-5alpha-stigmasta-8,14-diene-3,28-dione (2) and two new sucrose esters, 1',3,3',4',6'-pentakis-O-(3-methylbutanoyl)-beta-D-fructofuranosyl alpha-D-glucopyranoside (3) and 1',2,3',6,6'-pentakis-O-(3-methylbutanoyl)-beta-D-fructofuranosyl alpha-D-glucopyranoside (4), have been isolated from the stem bark of Vernonia guineensis. The structures of the new compounds were determined on the basis of spectroscopic evidence.
Assuntos
Sitosteroides/isolamento & purificação , Vernonia/química , Estrutura Molecular , Casca de Planta/químicaRESUMO
Two bitter stigmastane derivatives, vernoguinosterol (1) and vernoguinoside (2), have been isolated from the stem bark of Vernonia guineensis and their structures eludicated using spectroscopic methods. The new compounds exhibit trypanocidal activity.
Assuntos
Asteraceae/química , Sitosteroides/química , Sitosteroides/farmacologia , Tripanossomicidas/química , Tripanossomicidas/farmacologia , Trypanosoma brucei rhodesiense/efeitos dos fármacos , Animais , Avaliação Pré-Clínica de Medicamentos , Concentração Inibidora 50 , Conformação Molecular , Estrutura Molecular , Casca de Planta/química , Caules de Planta/química , Plantas Medicinais/química , Sitosteroides/isolamento & purificação , Tripanossomicidas/isolamento & purificaçãoRESUMO
Glabrescin, a daphnane diterpenoid, neoboutonin, a degraded diterpenoid with a novel skeleton, and neoglabrescins A and B, two rhamnofolane derivatives, have been isolated from the stem bark of Neoboutonia glabrescens Prain (Euphorbiaceae), together with the known tigliane derivative, baliospermin, and the known daphnane, montanin. Other constituents include squalene, 3-acetylaleuritolic acid, oleanolic acid and sitosterol, and the phenolic compounds 9-methoxy-1,7-dimethylphenanthrene and 2,3,8-tri-O-methylellagic acid. The structures were assigned on the basis of spectral studies and comparison with published literature data. The structures of neoglabrescins A and B were derived for their acetylated derivatives and, in the case of neoglabrescin A, confirmed by X-ray crystallographic analysis.
Assuntos
Diterpenos/isolamento & purificação , Euphorbiaceae/química , Cristalografia por Raios X , Diterpenos/química , Modelos Moleculares , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Casca de Planta/química , Caules de Planta/químicaRESUMO
Two new aromadendrane sesquiterpenoids (1ß,4ß,5ß,6α,7α,11S)-aromadendr-9-en-13,14-dioic acid (1) and (1ß,4ß,5ß,6α,7α,11S)-13-oxoaromadendr-9-en-14-oic acid (2) have been isolated from the stem bark of Alafia multiflora along with ß-sitosterol and ß-sitosterol glucoside. Their structures were established on the basis of spectroscopic analyses, including 1D and 2D NMR experiments (1H-1H COSY, NOESY, HSQC, HMBC). Compound 1 showed a weak growth inhibitory activity against the murine melanoma line B16F10 MTT.
Assuntos
Apocynaceae/química , Sesquiterpenos/isolamento & purificação , Animais , Linhagem Celular Tumoral , Espectroscopia de Ressonância Magnética , Melanoma Experimental/tratamento farmacológico , Camundongos , Casca de Planta/química , Caules de Planta/química , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Sesquiterpenos de GuaianoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Aerial parts of Acanthospermum hispidum D.C. are often used by traditional healers in Benin for various diseases and especially for malaria. AIM OF THE STUDY: To identify active compounds from extracts of Acanthospermum hispidum D.CV. leaves previously shown to possess antimalarial properties and analyse in vivo activity and toxicity of crude extracts. MATERIALS AND METHODS: Compounds were isolated from aerial part of Acanthospermum hispidum D.C. and structurally elucidated using extensive spectroscopic analysis. Antiplasmodial activity was evaluated in vitro against a chloroquine-sensitive strain of Plasmodium falciparum (3D7) using the measurement of the plasmodial lactate dehydrogenase activity and in vivo against Plasmodium berghei berghei by the 4-day suppressive test. Selectivity of extract and purified compounds on Plasmodium parasites were evaluated by using MTT test on J774 macrophage like murine cells and WI38 human normal fibroblasts and also against two other parasites: Trypanosoma brucei brucei and Leishmania mexicana mexicana. Acute and sub-acute toxicities of a crude extract were evaluated on mice. RESULTS: Two known sesquiterpenic lactones were isolated: 1 (15-acetoxy-8ß-[(2-methylbutyryloxy)]-14-oxo-4,5-cis-acanthospermolide) and 2 (9α-acetoxy-15-hydroxy-8ß-(2-methylbutyryloxy)-14-oxo-4,5-trans-acanthospermolide). 1 and 2 showed in vitro antiplasmodial activity against the chloroquine-sensitive strain (3D7) with IC(50) of 2.9±0.5 and 2.23±0.09µM respectively. Only 2 showed a high selectivity index (SI: 18.4) on Plasmodium compared to cytotoxicity against human fibroblasts cell line (WI38). 1 and 2 also showed interesting antiparasitic activities in vitro against Trypanosoma brucei brucei (IC(50) of 2.45±0.49 and 6.36±1.42µM respectively) and Leishmania mexicana mexicana (IC(50) of 0.94±0.05 and 2.54±0.19µM respectively). Furthermore, crude acidic water extract and fractions containing one of the two isolated compounds displayed a weak in vivo antimalarial activity against Plasmodium berghei berghei with a long half-life causing a delayed effect. In vivo acute (2000mg/kg) and sub-acute (1000mg/kg) toxicity tests on the crude acidic water extract did not show toxicity. CONCLUSION: Crude acidic water extract, fractions and pure isolated compounds from Acanthospermum hispidum showed promising in vitro antiplasmodial activity. Despite our study did not show in vivo acute and subacute toxicities of the crude acidic water extract, its weak in vivo antimalarial activity and the in vitro cytotoxicity of pure compounds and enriched extracts containing 1 and 2 indicate that the aerial parts of Acanthospermum hispidum should be used with caution for malaria treatments.