Synthesis and evaluation of new 4-oxoquinazolin-3(4H)-yl)benzoic acid and benzamide derivatives as potent antibacterial agents effective against multidrug resistant Staphylococcus aureus.
Bioorg Chem
; 83: 569-579, 2019 03.
Article
em En
| MEDLINE
| ID: mdl-30471579
ABSTRACT
Treatment of nosocomial and community acquired Staphylococcus aureus infections has become more challenging due to the egression of multi-drug resistance. This has spurred the need for rapid development of new therapeutic agents which can effectively negate the resistance mechanisms. In our current work, several new 4-oxoquinazolin-3(4H)-yl)benzoic acid and benzamide derivatives were synthesized and examined for their antimicrobial activity against ESKAP pathogen panel and pathogenic mycobacteria. In the primary screening, compounds 4a, 4b, 6'a, 6'b, 6'h, 6'i and 6'j were found to demonstrate selective and potent inhibitory activity against Staphylococcus aureus (MICsâ¯=â¯0.25-0.5⯵g/mL). When tested against Vero cells, all the compounds were found to be non toxic possessing favourable selectivity index (SIâ¯>â¯10), which encouraged us for carrying out further studies. Compound 6'a (SIâ¯>â¯40) was tested against a number of multiple clinical strains of multi-drug resistant S. aureus and was found to exhibit potent activity, irrespective of the resistant status of the strain. Besides, compound 6'a also exhibited concentration dependent bactericidal activity and synergized with the FDA approved drugs tested. The interesting results obtained suggest the potential utility of the newly synthesized compounds for treatment of multidrug resistant S. aureus infections.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Benzamidas
/
Benzoatos
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Quinazolinonas
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Staphylococcus aureus Resistente à Meticilina
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Antibacterianos
Limite:
Animals
Idioma:
En
Revista:
Bioorg Chem
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Índia