Antibiotic resistance is now a first-order health problem, which makes the development of new families of antimicrobials imperative. These compounds should ideally be inexpensive, readily available, highly active, and non-toxic. Here, we present the results of our investigation regarding the antimicrobial activity of a series of natural and synthetic polyamines with different architectures (linear, tripodal, and macrocyclic) and their derivatives with the oxygen-containing aromatic functional groups 1,3-benzodioxol, ortho/para phenol, or 2,3-dihydrobenzofuran. The new compounds were prepared through an inexpensive process, and their activity was tested against selected strains of yeast, as well as Gram-positive and Gram-negative bacteria. In all cases, the conjugated derivatives showed antimicrobial activity higher than the unsubstituted polyamines. Several factors, such as the overall charge at physiological pH, lipophilicity, and the topology of the polyamine scaffold were relevant to their activity. The nature of the lipophilic moiety was also a determinant of human cell toxicity. The lead compounds were found to be bactericidal and fungistatic, and they were synergic with the commercial antifungals fluconazole, cycloheximide, and amphotericin B against the yeast strains tested.

Antibiotic resistance is now a first-order health problem, which makes the development of new families of antimicrobials an imperative. These compounds should ideally be inexpensive, readily available, highly active and non-toxic. Here we present the results on the antimicrobial activity of a series of natural and synthetic polyamines with different architectures (linear, tripodal and macrocyclic) and their derivatives containing the oxygen containing aromatic functional groups 1,3-benzodioxol, ortho/para phenol or 2,3-dihydrobenzofuran. The new compounds were prepared through a non-expensive process and their activity was tested against selected strains of yeast, gram-positive and gram-negative bacteria. In all cases, the conjugated derivatives showed antimicrobial activity higher than the unsubstituted polyamines. Several factors, such as the overall charge at physiological pH, the lipophilicity and the topology of the polyamine scaffold were relevant to their activity. The nature of the lipophilic moiety was also determinant on human cell toxicity. The lead compounds showed to be bactericidal and fungistatic, and they were synergic with the commercial antifungals fluconazole, cycloheximide and amphotericin B against the yeast strains tested.