RESUMO
Three new sesquiterpenoid derivatives 1, 2, and 3 were isolated from Ferula ferulaeoides. To confirm the structure, compound 2 was also synthesized via a condensation reaction between compound 1 and 2,2-dimethoxypropane. The structures of these three compounds were elucidated by means of spectroscopic and chemical methods. Their antibacterial activity against drug-resistant Staphylococcus aureus strains were evaluated with MIC values in the range of 0.5-128 µg/mL. Compounds 1 and 3 were capable of inhibiting efflux of ethidium bromide using an in vitro assay. The cytotoxicity of the compounds was evaluated on cultured HEK293 cells, and none of them showed toxicity to HEK293 cells at a concentration of 125 µg/mL.
Assuntos
Antibacterianos/isolamento & purificação , Ferula/química , Sesquiterpenos/isolamento & purificação , Antibacterianos/química , Antibacterianos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Células HEK293 , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Staphylococcus aureus/efeitos dos fármacosRESUMO
In a project to characterise new antibacterial chemotypes from plants, hyperenone A and hypercalin B were isolated from the hexane and chloroform extracts of the aerial parts of Hypericum acmosepalum. The structures of both compounds were characterised by extensive one- and two-dimensional nuclear magnetic resonance (NMR) spectroscopy and were confirmed by mass spectrometry. Hyperenone A and hypercalin B exhibited antibacterial activity against multidrug-resistant strains of Staphylococcus aureus, with minimum inhibition concentration ranges of 2-128 mg/L and 0.5-128 mg/L, respectively. Hyperenone A also showed growth-inhibitory activity against Mycobacterium tuberculosis H37Rv and Mycobacterium bovis BCG at 75 mg/L and 100mg/L. Neither hyperenone A nor hypercalin B inhibited the growth of Escherichia coli and both were non-toxic to cultured mammalian macrophage cells. Both compounds were tested for their ability to inhibit the ATP-dependent MurE ligase of M. tuberculosis, a crucial enzyme in the cytoplasmic steps of peptidoglycan biosynthesis. Hyperenone A inhibited MurE selectively, whereas hypercalin B did not have any effect on enzyme activity.
Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Hypericum/química , Mycobacterium tuberculosis/efeitos dos fármacos , Peptídeo Sintases/antagonistas & inibidores , Extratos Vegetais/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Escherichia coli/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Testes de Sensibilidade Microbiana , Estrutura Molecular , Mycobacterium bovis/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Staphylococcus aureus/efeitos dos fármacosRESUMO
Two new norlignans, hyperiones A (1) and B (2), three new acylphloroglucinols, aspidinol C (3) and hyperaspidinols A (5) and B (6), the known compound aspidinol D (4), and the symmetrical dimeric xanthone hyperidixanthone (7) were isolated from Hypericum chinense. Their structures were established by spectroscopic analysis. In an antibacterial assay using a panel of multidrug-resistant (MDR) strains, compounds 3 and 4 exhibited promising activity against the NorA efflux protein overexpressing MDR Staphylococcus aureus strain SA-1199B with a minimum inhibitory concentration (MIC) of 2 µg/mL (8.4 µM) and 4 µg/mL (16.8 µM), respectively. The positive control antibiotic norfloxacin showed activity at MIC 32 µg/mL (100 µM).