RESUMO
Three new diterpenes, uprolide N (1), uprolide O (2), uprolide P (3) and a known one, dolabellane (4), were isolated from the CH2Cl2-MeOH extract of the gorgonian octocoral Eunicea succinea, collected from Bocas del Toro, on the Caribbean coast of Panama. Their structures were determined using spectroscopic analyses, including 1D and 2D NMR and high-resolution mass spectrometry (HRMS) together with molecular modeling studies. Compounds 1-3 displayed anti-inflammatory properties by inhibiting production of Tumor Necrosis Factor (TNF) and Interleukin (IL)-6 induced by lipopolysaccharide (LPS) in murine macrophages.
Assuntos
Antozoários/química , Diterpenos/química , Inflamação/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Animais , Diterpenos/administração & dosagem , Diterpenos/isolamento & purificação , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/induzido quimicamente , Inflamação/genética , Interleucina-6/biossíntese , Interleucina-6/genética , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Modelos Moleculares , Panamá , Extratos Vegetais/química , Células Tumorais Cultivadas , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/genéticaRESUMO
Two new compounds, 5-(11'(S)-hydroxy-8'-heptadecenyl)resorcinol (3) and 5-(12'(S)-hydroxy-8',14'-heptadecadienyl)resorcinol (4), were isolated from the leaves of Stylogyne turbacensis together with the known analogue metabolites 1 and 2. Compounds 3 and 4 showed the strongest activity in the leishmania assay, 7 and 3 microM, respectively, while compounds 1, 2, and 4 showed moderate activity against a drug-resistant strain of Trypanosoma cruzi with IC(50) values of 30, 25, and 22 microM, respectively. Additional testing in MCF-7 and NCI-H460 was performed for compounds 3 and 4. The structures of compounds 1-4 were elucidated using NMR, MS, and other spectroscopic data. The absolute stereochemistry of compounds 3 and 4 was also investigated using the Mosher ester approach. Peracetylated derivatives of these four metabolites were produced and their activities determined in the Trypanosoma cruzi assay.
Assuntos
Antiprotozoários/isolamento & purificação , Leishmania/efeitos dos fármacos , Plantas Medicinais/química , Primulaceae/química , Resorcinóis/isolamento & purificação , Trypanosoma cruzi/efeitos dos fármacos , Animais , Antiprotozoários/química , Antiprotozoários/farmacologia , Chlorocebus aethiops , Feminino , Humanos , Ressonância Magnética Nuclear Biomolecular , Panamá , Resorcinóis/química , Resorcinóis/farmacologia , Células VeroRESUMO
Three new flavonol arabinosides (2-4) were isolated from the young leaves of Calycolpus warszewiczianus. The structures were determined as myricetin-3-O-alpha-L-3' '-acetylarabinofuranoside (2), myricetin-3-O-alpha-L-3' ',5' '-diacetylarabinofuranoside (3), and 5-galloylquercetin-3-O-alpha-L-arabinofuranoside (4). Molecular structures were elucidated using NMR spectroscopy in combination with IR and MS data. Two known compounds, myricetin-3-O-alpha-L-arabinofuranoside (1) and (-)-epi-catechin (5), were also isolated. The compounds were tested in vitro against a chloroquine-resistant strain of Plasmodium falciparum, Leishmania mexicana, and Trypanosoma cruzi parasites. Compound 4 demonstrated weak activity against a chloroquine-resistant strain of P. falciparum (14.5 microM), whereas none of the compounds demonstrated activity against L. mexicana and T. cruzi at the concentrations of 40 and 50 microg/mL, respectively, and no cytotoxicity was detected against mammalian cells below 100 microg/mL.
Assuntos
Antimaláricos , Arabinose , Flavonóis , Myrtaceae/química , Plantas Medicinais/química , Animais , Antimaláricos/química , Antimaláricos/isolamento & purificação , Antimaláricos/farmacologia , Antiprotozoários/química , Antiprotozoários/isolamento & purificação , Antiprotozoários/farmacologia , Arabinose/análogos & derivados , Arabinose/química , Arabinose/isolamento & purificação , Arabinose/farmacologia , Cloroquina/farmacologia , Relação Dose-Resposta a Droga , Resistência a Medicamentos , Flavonóis/química , Flavonóis/isolamento & purificação , Flavonóis/farmacologia , Leishmania mexicana/efeitos dos fármacos , Estrutura Molecular , Panamá , Plasmodium falciparum/efeitos dos fármacos , Trypanosoma cruzi/efeitos dos fármacosRESUMO
Four new diterpenes (1-4) were isolated from the leaves of Myrospermum frutescens as minor constituents. Chagresnol (1), 6beta,18-diacetoxycassan-13,15-diene (2), and chagreslactone (3) possess cassane skeletons, while chagresnone (4) exhibits a cleistanthane skeleton. Molecular structures and their relative stereochemistries were elucidated using NMR spectroscopy in combination with UV, IR, and MS spectral data. Although compound 2 was previously reported as a synthetic product, we report its first isolation as a natural product. Derivative products (10-13) were obtained to test their activities against Chagas's disease. In addition, the absolute stereochemistry of the previously isolated cassane diterpene 5 from M. frutescens is presented.