Département de chimie moléculaire

The synthesis of 37 1-(1H-indol-3-yl)ethanamine derivs., including 12 new compds., was achieved through a series of simple and efficient chem. modifications. These indole derivs. displayed modest or no intrinsic anti-staphylococcal activity. By contrast, several of the compds. restored, in a concn.-dependent manner, the antibacterial activity of ciprofloxacin against Staphylococcus aureus strains that were resistant to fluoroquinolones due to overexpression of the NorA efflux pump. Structure-activity relationships studies revealed that the indolic aldonitrones halogenated at position 5 of the indole core were the most efficient inhibitors of the S. aureus NorA efflux pump. Among the compds., (Z)-N-benzylidene-2-(tert-butoxycarbonylamino)-1-(5-iodo-1H-indol-3-yl)ethanamine oxide led to a fourfold decrease of the ciprofloxacin min. inhibitory concn. against the SA-1199B strain when used at a concn. of 0.5 mg.L^-1. To the best of our knowledge, this activity is the highest reported to date for an indolic NorA inhibitor. In addn., a new antibacterial compd., tert-Bu (2-(3-hydroxyureido)-2-(1H-indol-3-yl)ethyl)carbamate, which is not toxic for human cells, was also found.