Add time:07/29/2019         Source:sciencedirect.com

The aminoacyl-tRNA synthetase (aaRS) class of enzymes is a validated target for antimicrobial development. Aminoacyl analogues of 5′-O-(N-l-aminoacyl)-sulfamoyladenosines are known to be potent inhibitors of aaRS, but whole cell antibacterial activity of these compounds is very limited, and poor penetration into bacteria has been proposed as the main reason for this. Aiming to find derivatives that better penetrate bacteria, we developed a simple and short method to prepare dipeptidyl-derivatives of 5′-O-(N-l-aminoacyl)-sulfamoyladenosines, and used this method to prepare 18 5′-O-(N-dipeptidyl)-sulfamoyladenosines. The antibacterial activity of these derivatives and a number of reference compounds against S. aureus, E. faecalis and E. coli was determined. Several of the new derivatives showed improved antibacterial activity and an altered spectrum of antibacterial activity.

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