Virtual Screening, Synthesis and Biological Evaluation of Streptococcus mutans Mediated Biofilm Inhibitors.
Molecules
; 27(4)2022 Feb 21.
Article
em En
| MEDLINE
| ID: mdl-35209243
ABSTRACT
Dental caries, a global oral health concern, is a biofilm-mediated disease. Streptococcus mutans, the most prevalent oral microbiota, produces extracellular enzymes, including glycosyltransferases responsible for sucrose polymerization. In bacterial communities, the biofilm matrix confers resistance to host immune responses and antibiotics. Thus, in cases of chronic dental caries, inhibiting bacterial biofilm assembly should prevent demineralization of tooth enamel, thereby preventing tooth decay. A high throughput screening was performed in the present study to identify small molecule inhibitors of S. mutans glycosyltransferases. Multiple pharmacophore models were developed, validated with multiple datasets, and used for virtual screening against large chemical databases. Over 3000 drug-like hits were obtained that were analyzed to explore their binding mode. Finally, six compounds that showed good binding affinities were further analyzed for ADME (absorption, distribution, metabolism, and excretion) properties. The obtained in silico hits were evaluated for in vitro biofilm formation. The compounds displayed excellent antibiofilm activities with minimum inhibitory concentration (MIC) values of 15.26-250 µg/mL.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Streptococcus mutans
/
Modelos Moleculares
/
Biofilmes
/
Antibacterianos
Tipo de estudo:
Diagnostic_studies
/
Screening_studies
Limite:
Humans
Idioma:
En
Revista:
Molecules
Assunto da revista:
BIOLOGIA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Paquistão