1α,2α-Epoxy-3ß-hydroxy oleanolic acid derivatives regulation of the metabolism, haemolysis and ß-lactamase gene expression in vitro and their structure-microbicidal activity relationship.
Bioorg Med Chem Lett
; 26(16): 3870-5, 2016 08 15.
Article
em En
| MEDLINE
| ID: mdl-27436581
ABSTRACT
Oleanolic acid (OA), one of the major pentacyclic triterpenes abundantly present in nature, is a promising compound with various biological activities, including anti-inflammatory, anti-ulcer, hepatoprotective, antidiabetic, fungicidal and antiparasitic properties. Therefore, a series of derivatives of 1α,2α-epoxy-3ß-hydroxyl oleanolic acid derivatives were designed and synthesized, and their antibacterial activities were investigated in vitro. Based on these results, the compounds with antibacterial activity were screened by RT-PCR to determine whether they can regulate the expression of genes related to metabolism, haemolysis, and ß-lactamase in vitro, and the structure-microbicidal activity relationship of each compound was analyzed. Our study shows that some of the modifications in the synthetic compounds, such as the introduction of an ortho-cyano-substituted benzyl group and a short chain alkyl ester at the 28-carboxyl, as well as the introduction of an acetyl group at the 3-hydroxyl group of ring A, could enhance antibacterial activity. This provides basic evidence for the optimization of 1α,2α-epoxy-3ß-hydroxyl oleanolic acid derivatives. The antibacterial mechanism of the active OA derivatives appears to involve the regulation of expression of metabolism-associated genes in Escherichia coli, haemolysis-associated genes in Bacillus subtilis, metabolism-related genes in Klebsiella pneumonia and ß-lactamase-associated genes in Acinetobacter baumannii. Some OA derivatives were bactericidal to three of the strains and appeared to regulate gene expression associated with metabolism, haemolysis, and ß-lactamase in vitro. These newly designed OA derivatives possess unique antibacterial activities and may be potentially useful for prophylactic or therapeutic intervention of bacterial infections.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Ácido Oleanólico
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Beta-Lactamases
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Antibacterianos
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
China