RESUMO
A new maltol derivative (2) along with three known maltol derivative (1) and flavonol glycosides (3 and 4) were isolated from the dried flowers of Sophora japonica. Based upon the results of combined spectroscopic methods, the structure of new compound (2) was determined to be maltol-3-O-(4'-O-cis-p-coumaroyl-6'-O-(3-hydroxy-3-methylglutaroyl))-ß-glucopyranoside, an isomer of 1. These compounds strongly inhibited the action of sortase A (SrtA) from Streptococcus mutans, a primary etiologic agent of human dental caries. The onset and magnitude of inhibition of the saliva-induced aggregation in S. mutans treated with compound 2 (4×IC50) were comparable to the behavior of untreated srtA-deletion mutant.
Assuntos
Aminoaciltransferases/antagonistas & inibidores , Proteínas de Bactérias/antagonistas & inibidores , Flores/química , Pironas/farmacologia , Sophora/química , Streptococcus mutans/efeitos dos fármacos , Aminoaciltransferases/genética , Aminoaciltransferases/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Cisteína Endopeptidases/genética , Cisteína Endopeptidases/metabolismo , Relação Dose-Resposta a Droga , Conformação Molecular , Pironas/química , Pironas/isolamento & purificação , Streptococcus mutans/crescimento & desenvolvimento , Streptococcus mutans/metabolismo , Relação Estrutura-AtividadeRESUMO
Na(+)/K(+)-adenosine triphosphatase (ATPase) inhibitors have considerable therapeutic potential against some heart diseases like congestive heart failure and cardiac arrhythmias. Through bioassay-guided separation of the leaf extract of Laurus nobilis, six acylated kaempferol glycosides (compounds 1-6) were isolated. Their structures were determined on the basis of spectroscopic analysis and comparison with reported data. All the isolates were subjected to in vitro bioassays to evaluate their inhibitory activities against Na(+)/K(+)-ATPase from porcine cerebral cortex and bacterial growth. These studies led to the identification of compounds 1-6 as potent Na(+)/K(+)-ATPase inhibitors, with IC(50) values in the range of 4.0 ± 0.1-10.4 ± 0.6 µM. These compounds also exhibited a broad spectrum of antibacterial activity. In particular, compounds 4 and 6 showed potent inhibitory activities against several bacterial strains, except Escherichia coli, with minimum inhibitory concentration (MIC) values in the range of 0.65-2.08 µg/mL. Thus, L. nobilis-derived acylated kaempferol glycosides may have a potential to be leads for the development of Na(+)/K(+) ATPase inhibitors (1-6) and antibacterial agents (4, 6).