New compounds for a good old class: Synthesis of two Β-lactam bearing cephalosporins and their evaluation with a multidisciplinary approach.
Bioorg Med Chem
; 28(4): 115302, 2020 02 15.
Article
en En
| MEDLINE
| ID: mdl-31932194
ABSTRACT
Antimicrobial resistance is spreading massively in the world and is becoming one of the main health threats of the 21st century. One of the possible strategies to overcome this problem is to modify the known classes of antibiotics in a rational way, with the aim of tuning their efficacy. In this paper, we present the synthesis and the evaluation of the biological activity of a series of two ß-lactam bearing cephalosporin derivatives, in which an additional isolated azetidinone ring, bearing different substituents, is joined to the classical cephalosporanic nucleus by a chain of variable length. A computational approach has been also applied in order to predict the molecular interactions between some representative derivatives and selected penicillin-binding proteins, the natural targets of ß-lactam antibiotics. All these derivatives are active against Gram-positive bacteria, with MIC100 comparable or even better than that of the reference antibiotic ceftriaxone, and show no or very low cytotoxic activity on different cell lines. Overall, these molecules appear to be able to exert their activity in particular against microorganisms belonging to some of the species more involved in the development of multidrug resistance.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Cefalosporinas
/
Beta-Lactamas
/
Bacterias Gramnegativas
/
Bacterias Grampositivas
/
Antibacterianos
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Italia