Discovery of Antibacterial Compounds with Potential Multi-Pharmacology against Staphylococcus Mur ligase Family Members by In Silico Structure-Based Drug Screening.
Molecules
; 29(16)2024 Aug 10.
Article
in En
| MEDLINE
| ID: mdl-39202871
ABSTRACT
Staphylococcus aureus (S. aureus) is a major bacterial infection in humans, leading to severe disease and causing death. The stagnation of antibiotic development in recent decades has made it difficult to combat drug-resistant infections. In this study, we performed an in silico structure-based drug screening (SBDS) targeting the S. aureus MurE (saMurE) enzyme involved in cell wall synthesis of S. aureus. saMurE is an enzyme that is essential for the survival of S. aureus but not present in humans. SBDS identified nine saMurE inhibitor candidates, Compounds 1-9, from a structural library of 154,118 compounds. Among them, Compound 2 showed strong antibacterial activity against Staphylococcus epidermidis (S. epidermidis) used as a model bacterium. Amino acid sequence homology between saMurE and S. epidermidis MurE is 87.4%, suggesting that Compound 2 has a similar inhibitory effect on S. aureus. Compound 2 showed an IC50 value of 301 nM for S. epidermidis in the dose-dependent growth inhibition assay. Molecular dynamics simulation showed that Compound 2 binds stably to both S. aureus MurD and S. aureus MurF, suggesting that it is a potential multi-pharmacological pharmacological inhibitor. The structural and bioactivity information of Compound 2, as well as its potential multiple-target activity, could contribute to developing new antimicrobial agents based on MurE inhibition.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Staphylococcus aureus
/
Drug Evaluation, Preclinical
/
Anti-Bacterial Agents
Limits:
Humans
Language:
En
Journal:
Molecules
Journal subject:
BIOLOGIA
Year:
2024
Document type:
Article
Affiliation country:
Japón
Country of publication:
Suiza