Reversal of Tetracycline Resistance in Escherichia coli by Noncytotoxic bis(Tryptophan)s

Nine bis(tryptophan) derivatives (BTs) and two control compounds were synthesized and tested for antimicrobial activity against two Escherichia coli strains and a Staphylococcus aureus strain. The effects of linker type, shape, and conformational rigidity were manifested in dramatic differences in altering tetracycline potency when coadministered with that antibiotic. A reversal of resistance was observed for an E. coli strain having a TetA efflux pump. Survival of mammalian cells was assayed with good result.