Novel pleuromutilin derivatives as antibacterial agents: synthesis, biological evaluation and molecular docking studies.
Bioorg Med Chem Lett
; 22(19): 6166-72, 2012 Oct 01.
Article
en En
| MEDLINE
| ID: mdl-22932314
ABSTRACT
Owing to the increasingly serious problems caused by multidrug resistance in community-acquired infection pathogens, it has become an urgent need to develop new classes of antibiotics for overcoming the resistance. In this paper, we describe the design and synthesis of novel pleuromutilin derivatives containing the (2-aminothiazol-4-yl)-4-methyl group, as well as their in vitro antibacterial activities against Gram-positive clinical bacteria. Most of the tested compounds displayed strong antibacterial activities against these methicillin-susceptible and methicillin-resistant bacteria. Particularly noteworthy compound 15 and its derivative 16e, both showed potent antibacterial properties (0.0625-0.5µg/mL) that are superior to amoxicillin and tiamulin. Molecular docking studies suggested that the amino thiazole ring on the side chains of the pleuromutilin derivatives can in general be accommodated near the mutilin core in the binding pocket, and thus play an important role in the activity of the whole molecule. The findings reported herein may provide a new insight into the design of novel pleuromutilin derivatives for human clinical use.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Staphylococcus epidermidis
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Resistencia a la Meticilina
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Staphylococcus aureus Resistente a Meticilina
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Antibacterianos
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2012
Tipo del documento:
Article