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 ( and ) 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 derivative showed the best potency with MICs of 0.5 µg/mL () and 1 µg/mL (), respectively. Several aminoguanidine hydrazone derivatives also showed good overall activity. Compounds , , and - displayed MICs of 4 µg/mL against both and . In the aminoguanidine hydrazone series, 3-(4-trifluoromethyl)-benzyloxy derivative showed the best potency against (MIC 1 µg/mL) but was far less active against (MIC 16 µg/mL). Compound and the -substituted derivative also showed promising results against two strains of methicillin-resistant (MRSA). These results provide new and potent structural leads for further antibiotic optimisation strategies.