Alkyl-guanidine Compounds as Potent Broad-Spectrum Antibacterial Agents: Chemical Library Extension and Biological Characterization

Nowadays,
the increasing of multidrug-resistant pathogenic bacteria
represents a serious threat to public health, and the lack of new
antibiotics is becoming a global emergency. Therefore, research in
antibacterial fields is urgently needed to expand the currently available
arsenal of drugs. We have recently reported an alkyl-guanidine derivative
(2), characterized by a symmetrical dimeric structure,
as a good candidate for further developments, with a high antibacterial
activity against both Gram-positive and Gram-negative strains. In
this study, starting from its chemical scaffold, we synthesized a
small library of analogues. Moreover, biological and in vitro pharmacokinetic characterizations were conducted on some selected
derivatives, revealing notable properties: broad-spectrum profile,
activity against resistant clinical isolates, and appreciable aqueous
solubility. Interestingly, 2 seems neither to select
for resistant strains nor to macroscopically alter the membranes,
but further studies are required to determine the mode of action.