RESUMEN
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).
Asunto(s)
Meliaceae/química , Tripanocidas/química , Tripanocidas/farmacología , Alquenos/química , Animales , Leishmania donovani/efectos de los fármacos , Limoninas/química , Espectroscopía de Resonancia Magnética , Ratones , Estructura Molecular , Corteza de la Planta/química , Células RAW 264.7 , Escopoletina/aislamiento & purificaciónRESUMEN
5-(2-ethylaminopropyl)benzofuran (5-EAPB) and 5,6-methylenedioxy-2-aminoindane (MDAI) are two new psychoactive substances (NPS) exhibiting MDMA-like properties. In this paper, we report the case of a 28-years old man, known as drug addict, found dead at home, with two unidentified powders next to him. External examination by the forensic pathologist was unremarkable but no autopsy was performed. Powders, blood and urine (which were the only samples available) were submitted to general unknown screening by high pressure liquid chromatography with a diode array detector (HPLC-DAD) and ultra high pressure liquid chromatography with a time-of-flight detector (UPLC-TOF-MS), after liquid-liquid extraction for biological samples, or simple dilution for powders. Analysis revealed 68% of MDAI in one powder and 87% of 5-EAPB in the other one. Significant levels of the same substances were found in blood (MDAI: 2.09 mg/L and 5-EAPB: 6.45 mg/L). The cause of death was therefore attributed to the consumption of these NPS since screening for other drugs of abuse and for alcohol was negative (oxazepam was found in urine only). 5-methylaminopropylbenzofuran (5-MAPB) and 5-aminopropylbenzofuran (5-APB) were also found in blood (0.089 and 0.546 mg/L, respectively) and urine (1.00 and 4.88 mg/L, respectively). In addition to the inherent complexity of NPS identification by itself, another analytical difficulty in this case was the identification of the EAPB positional isomer. Our routine screening methods were not able to distinguish the positional isomer, but an additional classical gas chromatography technique was able to make the distinction. Anyway, in our case, this issue was simplified thanks to the availability of a relatively pure powder that was analyzed by nuclear magnetic resonance (NMR).
Asunto(s)
Benzofuranos/envenenamiento , Indanos/envenenamiento , Psicotrópicos/envenenamiento , Adulto , Benzofuranos/análisis , Benzofuranos/química , Cromatografía de Gases , Cromatografía Líquida de Alta Presión , Humanos , Indanos/análisis , Indanos/química , Espectroscopía de Resonancia Magnética , Masculino , Espectrometría de Masas , Estructura Molecular , Psicotrópicos/análisis , Psicotrópicos/química , Detección de Abuso de Sustancias , Trastornos Relacionados con Sustancias/complicacionesRESUMEN
OBJECTIVES: The aim of the present study consisted in the isolation of flavonoids from the leaves of Bryonia alba L. and evaluation of their antioxidant activity and inhibition on peroxidase-catalysed reactions. METHODS: Flavonoids were isolated by preparative HPLC-DAD and their structures were elucidated by MS and NMR. Inhibitory effect was tested by the horseradish peroxidase and the myeloperoxidase assays. Cellular antioxidant assays consisted in testing the inhibitory activity on the reactive oxygen species released upon activation of neutrophils freshly isolated ex vivo from equine blood and of human monocytes-derived macrophages in vitro. Whole organism toxicity was assessed on zebrafish larvae. KEY FINDINGS: Four flavonoids (lutonarin, saponarin, isoorientin and isovitexin) were isolated. The performed assays showed significant antioxidant activity and inhibition for the peroxidase-catalysed reactions. Absence of cellular and zebrafish toxicity was confirmed. CONCLUSIONS: Bryonia alba L. leaves are particularly interesting for their flavonoids content and showed significant inhibitory effect on peroxidase-catalysed oxidation of substrates (Amplex Red and L012), as well as antioxidant/antiradical activity, proving that this species has a medicinal potential. Moreover, the present study highlights the absence of the toxicity of these leaves and offers though a novel perspective on the species, previously known as being toxic.
Asunto(s)
Antioxidantes/farmacología , Bryonia/química , Flavonoides/farmacología , Extractos Vegetales/farmacología , Animales , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Cromatografía Líquida de Alta Presión/métodos , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/aislamiento & purificación , Inhibidores Enzimáticos/farmacología , Flavonoides/química , Flavonoides/aislamiento & purificación , Células HL-60 , Caballos , Humanos , Macrófagos/efectos de los fármacos , Monocitos/citología , Peroxidasa/antagonistas & inhibidores , Extractos Vegetales/química , Hojas de la Planta , Especies Reactivas de Oxígeno/metabolismo , Pez CebraRESUMEN
OBJECTIVES: To explore the in-vitro and in-vivo antimalarial potential of caffeic acid and derivatives. METHODS: Two common phenolic acids (caffeic acid and chlorogenic acid) were evaluated for in-vitro and in-vivo antiplasmodial activity in comparison with some semi-synthetic derivatives that were synthesized. An in-vitro assay based on plasmodial lactate dehydrogenase activity, and the classical in-vivo 5-day suppressive test from Peters on an artemisinin-resistant Plasmodium berghei strain was used. Parasitic stage sensitivity to ethyl caffeate was determined in this work. KEY FINDINGS: Phenolic acid esters derivatives showed better antiplasmodial activity than corresponding phenolic acids. The derivative with the highest in-vitro activity being caffeic acid ethyl ester, exhibiting an IC50 = 21.9 ± 9.4 µm. Ethyl caffeate and methyl caffeate were then evaluated for antimalarial activity in vivo and ethyl caffeate showed a growth inhibition of 55% at 100 mg/kg. Finally, it seems that ethyl caffeate blocks the growth of young parasitic forms. CONCLUSIONS: Our study provides evidence for an antimalarial potential of caffeic acid derivatives which are common in several medicinal plants traditionally used against malaria. It also demonstrates the possibility to use such derivatives in the treatment of malaria.
Asunto(s)
Ácidos Cafeicos/farmacología , Ácido Clorogénico/farmacología , Animales , Antimaláricos/farmacología , Concentración 50 Inhibidora , Ratones , Pruebas de Sensibilidad Parasitaria , Plasmodium berghei/efectos de los fármacosRESUMEN
Due to the in vitro antiplasmodial activity of leaf extracts from Vernonia fimbrillifera Less. (Asteraceae), a bioactivity-guided fractionation was carried out. Three sesquiterpene lactones were isolated, namely 8-(4'-hydroxymethacrylate)-dehydromelitensin (1), onopordopicrin (2) and 8α-[4'-hydroxymethacryloyloxy]-4-epi-sonchucarpolide (3). Their structures were elucidated by spectroscopic methods (1D and 2D NMR and MS analyses) and by comparison with published data. The isolated compounds exhibited antiplasmodial activity with IC50 values ≤ 5 µg/mL. Cytotoxicity of the compounds against a human cancer cell line (HeLa) and a mouse lung epithelial cell line (MLE12) was assessed to determine selectivity. Compound 3 displayed promising selective antiplasmodial activity (SI > 10).
Asunto(s)
Antimaláricos/farmacología , Lactonas/farmacología , Vernonia/química , Animales , Antimaláricos/química , Línea Celular , Citotoxinas/farmacología , Evaluación Preclínica de Medicamentos/métodos , Células HeLa , Humanos , Concentración 50 Inhibidora , Lactonas/química , Espectroscopía de Resonancia Magnética , Ratones , Estructura Molecular , Extractos Vegetales/química , Plasmodium falciparum/efectos de los fármacos , Sesquiterpenos/química , Sesquiterpenos/farmacologíaRESUMEN
Bioactivity-guided fractionation of the ethyl acetate extract of the leaves of Poupartia borbonica led to the isolation of three new alkyl cyclohexenone derivatives 1-3, and named Poupartone A-C. The structures of the new compounds were elucidated by 1D and 2D NMR spectroscopic data analysis and MS, whereas calculated and experimental ECD spectra were used to define the absolute configurations. These compounds were active against 3D7 and W2 Plasmodium falciparum strains with IC50 values between 0.55 and 1.81 µM. In vitro cytotoxicity against WI38 human fibroblasts and the human cervical cancer cell line HeLa (WST-1 assay) showed that these compounds were also cytotoxic, but no hemolytic activity was observed for the extract and pure compounds. An in vivo antimalarial assay was performed on the major cyclohexenone using P. berghei-infected mice at a dose of 15 mg/kg/day ip. The assay revealed growth inhibition of 59.1 and 69.5% at days 5 and 7 postinfection, respectively, although some toxicity was observed. Zebrafish larvae were used as a model to determine the type of toxicity, and the results showed cardiac toxicity. The methanol extract was also studied, and it displayed moderate antiplasmodial properties in vitro. This extract contained the known flavonoids, quercetin, 3'-O-hydroxysulfonylquercetin, quercitrin, and isoquercitrin as well as ellagic acid, which showed high to low activity against the 3D7 P. falciparum strain.
Asunto(s)
Anacardiaceae/química , Antimaláricos/aislamiento & purificación , Antimaláricos/farmacología , Ciclohexanonas/aislamiento & purificación , Ciclohexanonas/farmacología , Malaria/tratamiento farmacológico , Animales , Antimaláricos/química , Bélgica , Ciclohexanonas/química , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Flavonoides/química , Flavonoides/aislamiento & purificación , Flavonoides/farmacología , Células HeLa , Humanos , Concentración 50 Inhibidora , Ratones , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Pruebas de Sensibilidad Parasitaria , Hojas de la Planta/química , Plasmodium berghei/efectos de los fármacos , Plasmodium falciparum/efectos de los fármacos , Quercetina/análogos & derivados , Quercetina/química , Quercetina/farmacología , Pez Cebra/embriologíaRESUMEN
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.
Asunto(s)
Antimaláricos/farmacología , Caesalpinia/química , Extractos Vegetales/farmacología , Plasmodium falciparum/efectos de los fármacos , Antimaláricos/química , Antimaláricos/aislamiento & purificación , Cloroquina/farmacología , Cromatografía Líquida de Alta Presión , Etnofarmacología , Guinea , Células HeLa , Humanos , Concentración 50 Inhibidora , Medicina Tradicional , Pruebas de Sensibilidad Parasitaria , Extractos Vegetales/química , Hojas de la Planta , Análisis EspectralRESUMEN
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.
Asunto(s)
Anacardiaceae/química , Antimaláricos/química , Antimaláricos/farmacología , Esteroides/farmacología , Evaluación Preclínica de Medicamentos/métodos , Ergosterol/análogos & derivados , Ergosterol/química , Ergosterol/aislamiento & purificación , Ergosterol/farmacología , Concentración 50 Inhibidora , Estructura Molecular , Corteza de la Planta/química , Extractos Vegetales/análisis , Extractos Vegetales/química , Extractos Vegetales/farmacología , Plasmodium falciparum/efectos de los fármacos , Esteroides/químicaRESUMEN
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.
Asunto(s)
Apocynaceae/química , Sesquiterpenos/aislamiento & purificación , Animales , Línea Celular Tumoral , Espectroscopía de Resonancia Magnética , Melanoma Experimental/tratamiento farmacológico , Ratones , Corteza de la Planta/química , Tallos de la Planta/química , Sesquiterpenos/química , Sesquiterpenos/farmacología , Sesquiterpenos de GuayanoRESUMEN
As part of our continuing research for anticancer compounds from the Walloon Region forest, EtOAc extract from Carpinus betulus leaves was phytochemically studied, leading to the bioguided isolation of pheophorbide a, which is responsible of anticancer properties of C. betulus young leaves. This compound was identified using nuclear magnetic resonance and mass spectrophotometric data and comparison with a commercial standard. Evaluation of the growth inhibitory activities of pheophorbide a using MTT colorimetric assay and phase-contrast microscopy in various human cancer cell lines confirmed the photoactivable properties of this compound. Our research showed, for the first time, the presence of pheophorbide a, a chlorophyll derived compound, which we quantified in high quantities in young leaves of C. betulus. This is in contrast with the literature which generally describes pheophorbide a as a catabolic product of chlorophyll, then preferentially present in old leaves.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Betulaceae/química , Hojas de la Planta/química , Acetatos/química , Línea Celular Tumoral , Fraccionamiento Químico/métodos , Clorofila/análogos & derivados , Clorofila/química , Clorofila/farmacología , Cromatografía Líquida de Alta Presión , Humanos , Concentración 50 Inhibidora , Espectroscopía de Resonancia Magnética , Microscopía de Contraste de Fase , Extractos Vegetales/química , Extractos Vegetales/farmacologíaRESUMEN
Forty-eight extracts from 16 common Belgian trees from the Walloon Region forest were evaluated for in vitro growth inhibitory activity against the human LoVo colon cancer, PC3 prostate cancer, and U373 glioblastoma cell lines. Our study was performed with the aim of selecting plant candidates in order to later isolate new anticancer compounds from an easily affordable tree material. Extracts from Alnus glutinosa (stem bark), Carpinus betulus (leaves and stem bark), Castanea sativa (stem bark), Fagus sylvatica (leaves), Ilex aquifolium (leaves), Larix decidua (leaves), Quercus petraea (stem bark), and Quercus robur (leaves) showed for the first time potent in vitro growth inhibitory activity and could become easily affordable sources of potential new anticancer agents. Root extracts from Robinia pseudoacacia, already known for containing cytotoxic lectins, also showed interesting activity.