Bioactive amide and -aminophosphonate inhibitors for methicillin-resistant Staphylococcus aureus (MRSA)

摘要

Scaffolds of 2-acylamino-1,3,4-oxadiazole have been recently developed as transglycosylase inhibitors against MRSA. In the present study, structure-activity relationships of new derivatives of 2-acylamino-1,3,4-oxadiazole were explored with focus on the substitution of the aromatic rings. The in vitro antibacterial activity of these compounds against MRSA strain was evaluated using agar disc diffusion method. These inhibitors have an amide linker between 1,3,4-oxadiazole ring and the aromatic ring B. The role of this linker on the bioactivity of the compounds was also studied. The results showed promising series of 2--aminophosphonate-1,3,4-oxadiazole as inhibitors for MRSA strain. Both series revealed two structural features which appear to be essential for anti-MRSA activities, the first one is the incorporation of two electron-withdrawing groups at meta- and para- positions within aromatic ring B which contributed to a higher activity against MRSA strain. The second is the new -aminophosphonate linker serving as bio-isosteric analogue of the corresponding amide linker and giving comparable results with the amide derivatives.