Azobenzene as Antimicrobial Molecules

Abstract

Azo molecules, characterized by the presence of a -N=N- double bond, are widely used in various fields due to their sensitivity to external stimuli, ch as light. The emergence of bacterial resistance has pushed research towards designing new antimicrobial molecules that are more efficient than those currently in use. Many authors have attempted to exploit the antimicrobial activity of azobenzene and to utilize their photoisomerization for selective control of the bioactivities of antimicrobial molecules, which is necessary for antibacterial therapy. This review will provide a systematic and consequential approach to coupling azobenzene moiety with active antimicrobial molecules and drugs, including small and large organic molecules, such as peptides. A selection of significant cutting-edge articles collected in recent years has been discussed, based on the structural pattern and antimicrobial performance, focusing especially on the photoactivity of azobenzene and the design of smart materials as the most targeted and desirable application.

Red-shifted and pH-responsive imidazole-based azo dyes with potent antimicrobial activity

“…5 An additional interest in incorporating heterocyclic moieties into the azo dye scaffold is due to the improved bioactivity of the conjugated derivatives. 4,6,7 Among the different heterocycles, the imidazole nucleus has become one of the most important synthons in medicinal chemistry due to its broad range of chemical and biological properties. 8 Its particular relevance in the design of new imidazole-based antifungal agents 9,10 is another important area of research since the development of antimicrobial resistance, the emergence of new pathogens and the spread of the existing ones represent a global crisis.…”

“…They also offer broader structural diversity, basic sites and H-bonding interactions 5 . An additional interest in incorporating heterocyclic moieties into the azo dye scaffold is due to the improved bioactivity of the conjugated derivatives 4,6,7 . Among the different heterocycles, imidazole nucleus has become one of the most important synthons in medicinal chemistry due to its broad range of chemical and biological properties 8 .…”

Azobenzene derivatives with activity against drug‐resistant Candida albicans and Candida auris

“…[23] This basic structure can be found in various compounds with antimicrobial potential. [24] Among others, antimicrobial substances were synthesized in which this azobenzene core was modified only by alkyl chains (Figure 1b) as well as amphiphilic cationic azobenzene derivatives (Figure 1c). [17][18][19][20] Three cationic amphiphilic azobenzene bromide salts (5a-c), which have already been investigated as photoliquefiable ionic crystals, [21,22] and two structurally similar compounds (5d,e) were synthesized and tested for their activity against different C. albicans and C. auris strains (Scheme 1).…”

“…[ 23 ] This basic structure can be found in various compounds with antimicrobial potential. [ 24 ] Among others, antimicrobial substances were synthesized in which this azobenzene core was modified only by alkyl chains (Figure 1b) as well as amphiphilic cationic azobenzene derivatives (Figure 1c). [ 17‐20 ]…”

Light-Switchable Membrane Permeability in Giant Unilamellar Vesicles

“…Molecules containing the azobenzene group can change their geometry from trans (E form, thermodynamically more stable) to cis (Z form) when irradiated by UV light (λ ~365 nm) and switch back to their original form via thermal relaxation or if irradiated with blue (λ ~465 nm) or visible light, as shown in Figure 1a. So far, azobenzene moieties have been successfully integrated into (i) receptors and ion channels [23,24], (ii) transporters and ion pumps [25], (iii) enzymatic ligands and inhibitors [25], (iv) DNA [26], (v) antimicrobics [27], (vi) prodrugs and drug delivery systems [28], allowing for their remote photoactivation and/or photomodulation with high spatial and temporal resolutions. Despite the biomedical applications of synthetic photoswitches still being in their preliminary stages, their efficacy has been demonstrated at the cellular level and, in some cases, on animal models, for the treatment of microbial infection, diabetes, cancer, pain, and blindness, providing evidence of their biocompatibility and for promising therapeutical applications in the near future [25].…”