Structure–activity relationship of the cinnamamide family of antibiotic potentiators for methicillin-resistant Staphylococcus aureus (MRSA). Issue 12 (22nd November 2018)

• Record Type: Journal Article
• Authors: Speri, Enrico; Fishovitz, Jennifer; Mobashery, Shahriar
• Is Part Of: MedChemComm. Volume 9:Issue 12(2018)
• Page Start: 2008
• Page End: 2016
• Publication Date: 2018-11-22
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19
• DOI: 10.1039/c8md00479j
• Languages: English
• ISSNs: 2040-2503

Abstract

Abstract : MIC of oxacillin against S. aureus (MRSA252 strain) reduced from 256 μg mL −1 to 2 μg mL −1 . Abstract : Methicillin-resistant Staphylococcus aureus (MRSA) is a global public health threat. MRSA has evolved a complex set of biochemical processes that mobilize the organism for inducible resistance on challenge by β-lactam antibiotics. Interfering pharmacologically with this machinery has the potential to reverse the β-lactam-resistance phenotype, whereby susceptibility to obsolete antibiotics would be restored. We describe herein our discovery of one class of such agents, the cinnamamide family of antibiotic potentiators. A hit compound of the class (compound1 ) showed modest potentiation of the activity of oxacillin, a penicillin antibiotic, against an MRSA strain. A total of 50 analogues of compound1 were prepared and screened. Seven of these compounds showed more dramatic potentiation of the antibacterial activity, which lowered the minimal-inhibitory concentrations (MICs) for the antibiotic by as much as 64- to 128-fold.