Antimicrobial Properties of New Polyamines Conjugated with Oxygen-Containing Aromatic Functional Groups

Abstract

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.

New Water-Soluble (Iminomethyl)benzenesulfonates Derived from Biogenic Amines for Potential Biological Applications

“…In this study, we proposed selecting BAs as reagents for synthesizing new SBs. It should be noted that the antibacterial properties of BAs are discussed in the literature [20][21][22]. The SBs obtained and the reagents (BAs, 2-FBS, and 3-FBS) were individually tested as an antibacterial agent against E. coli and S. aureus.…”

“…Moreover, the multiple activities induced by polyamines due to their interaction with different biological targets support the proposal of the polyamine skeleton as a universal model for further modification. According to Inclán et al [20], polyamine research has become an essential field for drug development. Their potential application has been studied as anticancer and antiproliferative agents, agonist-antagonist receptor ligands, or antiparasitic compounds.…”

Spider and Wasp Acylpolyamines: Venom Components and Versatile Pharmacological Leads, Probes, and Insecticidal Agents

“…The modular polyamine backbone allowed for preparing long linear derivatives with a broad spectrum of antimicrobial activity against multidrug-resistant bacteria [ 86 ]. Polyamines with diverse molecular architecture (linear, tripodal, and macrocyclic) and their derivatives with aromatic functional groups, such as 1,3-benzodioxol, ortho- and -para phenol, or 2,3-dihydrobenzofuran, indicated that the topology of the polyamine scaffold is essential for the antimicrobial activity of conjugates [ 87 ]. From the hemocytes of the tarantula spider Acanthoscurria gomesiana , the bis-acyl polyamine spermidine with antimicrobial and immunomodulatory activity was characterized, and its mechanism of action has been investigated in molecular detail [ 88 , 89 ].…”