Drug efficacy of novel 3-O-methoxy-4-halo disubstituted 5,7-dimethoxy chromans; evaluated via DNA gyrase inhibition, bacterial cell wall lesion and antibacterial prospective.
Bioorg Med Chem
; 26(12): 3438-3452, 2018 07 23.
Article
in En
| MEDLINE
| ID: mdl-29803359
ABSTRACT
In this study, novel 3-O-methoxy-4-halo, disubstituted-5,7-dimethoxy chromans with bacterial cell wall degrading potentials were synthesized, characterized and evaluated as DNA gyrase inhibitors and antibacterial agents. Compounds were showed a broad spectrum of antimicrobial activity against both Gram+ve bacteria (S. aureus (MTCC 3160), C. diphtheriae (MTCC 116), S. pyogenes (MTCC 442)) and Gram-ve bacteria (E. coli (MTCC 443), P. aeruginosa (MTCC 424), K. pneumoniae (MTCC 530)). Further, a molecular docking study was carried out to get more insight into the binding mode of present study compounds to target proteins (PDB ID 2XCT (S. aureus DNA gyrase A), PDB ID 3G75 (S. aureus DNA gyrase B), PDB ID 3L7L (Teichoic acid polymerase). In the results, 14â¯>â¯20â¯>â¯24â¯>â¯12â¯>â¯18â¯>â¯17 were found as the most active against almost all executed activities in this study. The predicted Lipinski's filter scores, SAR, pharmacokinetic/pharmacodynamics, and ADMET properties of these compounds envisioned the druggability prospects and the necessity of further animal model evaluations of 3-O-methoxy-4-halo disubstituted 5,7-dimethoxy chromans to establish them as an effective and future antibiotics.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Chromans
/
DNA Gyrase
/
Topoisomerase II Inhibitors
/
Anti-Bacterial Agents
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Bioorg Med Chem
Year:
2018
Document type:
Article