Novel Schiff base-bridged multi-component sulfonamide imidazole hybrids as potentially highly selective DNA-targeting membrane active repressors against methicillin-resistant Staphylococcus aureus.
Bioorg Chem
; 107: 104575, 2021 02.
Article
em En
| MEDLINE
| ID: mdl-33385978
ABSTRACT
A new type of Schiff base-bridged multi-component sulfonamide imidazole hybrids with antimicrobial potential was developed. Some target compounds showed significant antibacterial potency. Observably, butylene hybrids 4h exhibited remarkable inhibitory efficacy against clinical MRSA (MIC = 1 µg/mL), but had no significant toxic effect on normal mammalian cells (RAW 264.7). The highly active molecule 4h was revealed by molecular modeling study that it could insert into the base-pairs of DNA hexamer duplex and bind with the ASN-62 residue of human carbonic anhydrase isozyme II through hydrogen bonding. Furthermore, further preliminary antibacterial mechanism experiments confirmed that compound 4h could effectively interfere with MRSA membrane and insert into bacterial DNA isolated from clinical MRSA strains through non-covalent bonding to produce a supramolecular complex, thus exerting its strong antibacterial efficacy by impeding DNA replication. These findings strongly implied that the highly active hybrid 4h could be used as a potential DNA-targeting template for the development of valuable antimicrobial agent.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sulfonamidas
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DNA Bacteriano
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Staphylococcus aureus Resistente à Meticilina
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Imidazóis
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Antibacterianos
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article