Design and synthesis of novel N-methyl-N-(2,4,6-trimethoxybenzyl)cinnamamide derivatives as CrtN inhibitors for treatment of infectious diseases

Abstract

CrtN has been identified as an appealing target for treatment of pigmented staphylococcus aureus infections. A novel of N-methyl-N-(2,4,6-trimethoxybenzyl)cinnamamide derivatives as CrtN inhibitors based on the structure of naftifine (NTF) were designed and synthesis, and evaluate for their pigment inhibition activities in S.aureus Newman. Out of them, compound 6q represented the potent activity against the pigment and CrtN enzyme with the IC50 value of 23.1 nM and 233.1 nM, respectively, which was superior to that of NTF. Meanwhile, compound 6q could make S. aureus more susceptible to immune clearance. It was indicated that replacement of the naphthalenyl ring in NTF with the phloroglucinol ring is an effective strategy to develop new CrtN inhibitors.

Keywords

• CrtN
• Pigment inhibition
• Immune clearance
• S.aureus Newman