RESUMO
Two new isopimaranes, 19-methylmalonyloxy-ent-isopimara-8(9),15-diene (5) and 19-malonyloxy-ent-isopimara-8(9),15-diene (6), were isolated using bioassay-guided fractionation of the CH(2)Cl(2)-MeOH (1:1) extract of the aerial part of Calceolaria pinifolia along with eight other diterpenes (1-4, 7-10) and two triterpenes (11, 12). All compounds were assayed against Staphylococcus aureus (SA), methicillin-resistant S. aureus (MRSA), Bacillus subtilis (BS), and Escherichia coli (EC). 4-Epi-dehydroabietinol (2) and ent-isopimara-9(11),15-diene-19-ol (8) were found to be active against MRSA with MIC values of 8 and 2 microgram/mL, respectively. Mechanistic studies of 8 in BS suggested rapid and nonspecific inhibition of uptake and incorporation of radiolabeled precursors into DNA, RNA, and protein consistent with membrane-damaging effects in bacteria. Compound 8 did not afford protection against an acute infection with SA in mice.
Assuntos
Antibacterianos/isolamento & purificação , Diterpenos/isolamento & purificação , Plantas Medicinais/química , Scrophulariaceae/química , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Argentina , Bacillus subtilis/efeitos dos fármacos , Diterpenos/química , Diterpenos/farmacologia , Eritrócitos/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Feminino , Humanos , Resistência a Meticilina , Camundongos , Testes de Sensibilidade Microbiana , Conformação Molecular , Estrutura Molecular , Staphylococcus aureus/efeitos dos fármacosRESUMO
Four new alkylene resorcinols, (Z,Z)-5-(trideca-4,7-dienyl)resorcinol (1), (Z,Z,Z)-5-(trideca-4,7,10-trienyl)resorcinol (2), (Z,Z,E)-5-(trideca-4,7,10-trienyl)resorcinol (3), and (Z)-5-(trideca-4-enyl)resorcinol (4), were isolated from the MeOH-CH(2)Cl(2) extract of Lithraea molleoides. The structures of these compounds were determined by one- and two-dimensional NMR including selective decoupling experiments. In vitro all four compounds showed strong paralyzing effects on the nematode Caenorhabditis elegans at concentrations between 6 and 50 microg/mL, whereas the activity of compounds 1 and 2 against the nematode Trichostrongylus colubriformis was less pronounced and no activity against this nematode was observed for compounds 1-4 in a rodent model.