RESUMO
Seven benzo[c]phenanthridines, synthetic or isolated from Zanthoxylum rhoifolium root bark, were evaluated against Leishmania amazonensis axenic amastigotes. Five of them were considered leishmanicidal, with IC50 values ranging from 0.03 to 0.54 µM, and were evaluated on intramacrophagic amastigotes of L. amazonensis. Chelerythrine displayed the best activity (IC50=0.5 µM), which was in the same range as the reference compound amphotericin B (IC50=0.4 µM). In vivo studies with chelerythrine, avicine, and fagaridine on a model of mice cutaneous leishmaniasis resulted in the identification of fagaridine as the most active compound. Fagaridine decreased the parasitic burden more than 50% at the 3rd and 6th weeks after the end of treatment.
Assuntos
Leishmania/efeitos dos fármacos , Leishmaniose Cutânea/tratamento farmacológico , Fenantridinas/farmacologia , Extratos Vegetais/farmacologia , Zanthoxylum/química , Animais , Benzofenantridinas/química , Benzofenantridinas/isolamento & purificação , Benzofenantridinas/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Humanos , Concentração Inibidora 50 , Leishmaniose Cutânea/parasitologia , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Parasitária , Fenantridinas/química , Fenantridinas/isolamento & purificação , Casca de Planta/química , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Raízes de Plantas/química , Plantas MedicinaisRESUMO
A photostability study of Valsartan (VAL) is reported. Exposure of the drug to UV-vis radiation (λ > 320 nm) yielded two previously unknown compounds, which were detected by HPLC. Preparative amounts of the new potential degradation products (DP-1 and DP-2) were obtained by submitting VAL bulk drug to extensive photodegradation. The impurities were isolated by preparative normal phase column chromatography. Analytical information from the infrared, nuclear magnetic resonance and mass spectral data of the degradation products revealed their structures as N-[2'-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-N-isobutylpentanamide (DP-1) and N-(diazirino[1,3-f]phenanthridin-4-ylmethyl)-N-isobutylpentanamide (DP-2). DP-1 arose from decarboxylation of VAL, while DP-2 results from further loss of nitrogen from the tetrazole motif of DP-1, with concomitant cyclization to yield a tetracyclic diazacyclopropene derivative.
Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/química , Azirinas/isolamento & purificação , Contaminação de Medicamentos , Fenantridinas/isolamento & purificação , Fotólise , Tetrazóis/química , Tetrazóis/isolamento & purificação , Valina/análogos & derivados , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos da radiação , Bloqueadores do Receptor Tipo 1 de Angiotensina II/normas , Cromatografia Líquida de Alta Pressão/instrumentação , Cromatografia Líquida de Alta Pressão/métodos , Estabilidade de Medicamentos , Espectroscopia de Ressonância Magnética/instrumentação , Espectroscopia de Ressonância Magnética/métodos , Estrutura Molecular , Espectroscopia de Infravermelho com Transformada de Fourier/instrumentação , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Tetrazóis/efeitos da radiação , Tetrazóis/normas , Valina/química , Valina/efeitos da radiação , Valina/normas , ValsartanaRESUMO
The alkaloids lycorine, 1-O-acetyllycorine and ismine were isolated from the basic dichloromethane-soluble fraction of Crinum x powellii "Albu m" bulbs. The alkaloid structures were established by physical and spectroscopic analyses, including 1D NMR techniques and GC-MS analysis. The three alkaloids are reported for the first time for this hybrid. Additionally, the three alkaloids isolated were tested against a mechanism-based bioassay utilizing genetically engineered mutants of the yeast Saccharomyces cerevisiae strains RAD+, RAD52Y and RS321 where lycorine was the only alkaloid that displayed moderate topoisomerase I inhibitory activity.
Assuntos
Alcaloides/isolamento & purificação , Crinum/química , Inibidores Enzimáticos/isolamento & purificação , Extratos Vegetais/química , Inibidores da Topoisomerase , Alcaloides/química , Alcaloides/farmacologia , Alcaloides de Amaryllidaceae/química , Alcaloides de Amaryllidaceae/isolamento & purificação , Alcaloides de Amaryllidaceae/farmacologia , Compostos de Anilina/química , Compostos de Anilina/isolamento & purificação , Compostos de Anilina/farmacologia , Cromatografia em Camada Fina , Inibidores Enzimáticos/farmacologia , Metanol , Mutagênese , Fenantridinas/química , Fenantridinas/isolamento & purificação , Fenantridinas/farmacologia , Extratos Vegetais/isolamento & purificação , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/genéticaRESUMO
Fractionation of the chloroform extract from the aerial part of Argemone mexicana led to the isolation of two benzophenanthridine-type alkaloids, N-demethyloxysanguinarine and pancorine; three benzylisoquinoline-type alkaloids, (+)-1,2,3,4-tetrahydro-1-(2-hydroxymethyl-3,4-dimethoxyphenylmethyl)-6,7-methylenedioxyisoquinoline, (+)-higenamine and (+)-reticuline. Among them, N-demethyloxysanguinarine is a new compound, and (+)-1,2,3,4-tetrahydro-1-(2-hydroxymethyl-3,4-dimethoxyphenylmethyl)-6,7-methylenedioxy-isoquinoline was isolated form a natural source for the first time, to which was assigned a trivial name, (+)-argenaxine. In addition, six known non-alkaloidal compounds were also isolated and identified. All compounds were characterized on the basis of their spectral data and chemical evidences. Some isolated alkaloids from this species were evaluated for their cytotoxicity to human nasopharyngeal carcinoma (HONE-1) and human gastric cancer (NUGC) cell lines. Chelerythrine was found to exhibit significant activity against NUGC cell line, while angoline inhibited both types. (+)-Argenaxine showed moderate activity against the NUGC cell line.
Assuntos
Alcaloides/toxicidade , Argemone/química , Sobrevivência Celular/efeitos dos fármacos , Isoquinolinas/toxicidade , Fenantridinas/isolamento & purificação , Fenantridinas/toxicidade , Componentes Aéreos da Planta/química , Alcaloides/química , Alcaloides/isolamento & purificação , Humanos , Isoquinolinas/química , Isoquinolinas/isolamento & purificação , Modelos Moleculares , Estrutura Molecular , Neoplasias Nasofaríngeas , Fenantridinas/química , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Neoplasias Gástricas , Células Tumorais CultivadasRESUMO
Two quinoline alkaloids, (-)-R-geilbalansine (1) and hyemaline (2), as well as aromatic amide, N-[2-(3,4-dimethoxyphenyl)-2-methoxyethyl)-2-methoxyethyl]benzamide (O-methylbalsamide) (3), were isolated as new natural products from the stem barks of Zanthoxylum hyemale, together with seven known compounds. Their structures were determined on the basis of spectroscopic data (IR, (1)H- and (13)C-NMR, MS). In addition, the antispasmodic activity of the crude extract of Z. hyemale and three other more abundant isolated compounds (4, 5 and 10) were studied in two different antispasmodic test models on isolated rat ileum and only the crude ethanolic extract presented antispasmodic activity.