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Molecules ; 26(11)2021 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-34071703

RESUMEN

Staphylococcus aureus (S. aureus) is a major human pathogen that requires new antibiotics with unique mechanism. A new pleuromutilin derivative, 14-O-[(4,6-Diamino-pyrimidine-2-yl) thioacetyl] mutilin (DPTM), has been synthesized and proved as a potent antibacterial agent using in vitro and in vivo assays. In the present study, DPTM was further in vitro evaluated against methicillin-resistant Staphylococcus aureus (MRSA) isolated from dairy farms and outperformed tiamulin fumarate, a pleuromutilin drug used for veterinary. Moreover, a murine skin wound model caused by MRSA infection was established, and the healing effect of DPTM was investigated. The results showed that DPTM could promote the healing of MRSA skin infection, reduce the bacterial burden of infected skin MRSA and decrease the secretion of IL-6 and TNF-α inflammatory cytokines in plasma. These results provided the basis for further in-depth drug targeted studies of DPTM as a novel antibacterial agent.


Asunto(s)
Antibacterianos/farmacología , Cetonas/química , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Compuestos Policíclicos/química , Animales , Bovinos , Citocinas/metabolismo , Diterpenos/farmacología , Diseño de Fármacos , Técnicas In Vitro , Inflamación , Interleucina-6/metabolismo , Leucocitos/metabolismo , Ratones , Ratones Endogámicos BALB C , Pruebas de Sensibilidad Microbiana , Leche/microbiología , Simulación del Acoplamiento Molecular , Piel/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Factor de Necrosis Tumoral alfa/biosíntesis , Cicatrización de Heridas , Pleuromutilinas
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