Antimicrobial Properties of New Polyamines Conjugated with Oxygen-Containing Aromatic Functional Groups
Mario Inclán,
Neus Torres Hernández,
Alejandro Martínez Serra,
Gonzalo Torrijos Jabón,
Salvador Blasco,
Cecilia Andreu,
Marcel lí del Olmo,
Beatriz Jávega,
José-Enrique O’Connor,
Enrique García-España
Affiliations
Mario Inclán
Institute of Molecular Science, University of Valencia, 46980 Valencia, Spain
Neus Torres Hernández
Institute of Molecular Science, University of Valencia, 46980 Valencia, Spain
Alejandro Martínez Serra
Institute of Molecular Science, University of Valencia, 46980 Valencia, Spain
Gonzalo Torrijos Jabón
Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, University of Valencia, 46100 Valencia, Spain
Salvador Blasco
Institute of Molecular Science, University of Valencia, 46980 Valencia, Spain
Cecilia Andreu
Departament de Química Orgànica, Facultat de Farmàcia, University of Valencia, 46100 Valencia, Spain
Marcel lí del Olmo
Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, University of Valencia, 46100 Valencia, Spain
Beatriz Jávega
Laboratory of Cytomics, Joint Research Unit CIPF-UVEG, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Valencia, 46010 Valencia, Spain
José-Enrique O’Connor
Laboratory of Cytomics, Joint Research Unit CIPF-UVEG, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Valencia, 46010 Valencia, Spain
Enrique García-España
Institute of Molecular Science, University of Valencia, 46980 Valencia, Spain
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.
