Synthesis and in vitro antimicrobial SAR of benzyl and phenyl guanidine and aminoguanidine hydrazone derivatives

A series of benzyl, phenyl guanidine and aminoguandine hydrazone derivatives was designed and in vitro antibacterial activities against two different bacterial strains (Staphylococcus aureus and Escherichia coli) were determined. Several compounds showed potent inhibitory activity against the bacterial strains evaluated, with minimal inhibitory concentration (MIC) values in the low μg/mL range. Of all guanidine derivatives, 3-[2-chloro-3-(trifluoromethyl)]-benzyloxy deriva-tive 9m showed the best potency with MICs of 0.5 μg/mL (S. aureus) and 1 μg/mL (E. coli), respec-tively. Several aminoguanidine hydrazone derivatives also showed good overall activity. Com-pounds 10a, 10j and 10r-s displayed MICs of 4 μg/mL against both S. aureus and E. coli. In the ami-noguanidine hydrazone series, 3-(4-trifluoromethyl)-benzyloxy derivative 10d showed the best po-tency against S. aureus (MIC 1 μg/mL), but was far less active against E. coli (MIC 16 μg/mL). Com-pound 9m and the para-substituted derivative 9v also showed promising results against two strains of methicillin-resistant Staphylococcus aureus (MRSA). These results provide new and potent struc-tural leads for further antibiotic optimisation strategies.