“…This concept is based on the naturally occurring sideromycin antibiotics that mimic siderophores to gain intracellular access (Braun et al, 2009). Over the past three decades, numerous conjugates linking a siderophore or a siderophore mimic to different antibiotics via a linker molecule have been synthesized with varying degrees of antimicrobial efficacy (Möllmann et al, 2009;Wencewicz et al, 2009;Zeng et al, 2012;Fardeau et al, 2014). This approach, known as the 'Trojan horse' strategy, has been the subject of several reviews (including those by de Carvalho & Fernandes, 2014;Gó rska et al, 2014;Mislin & Schalk, 2014).…”
Section: Novel Therapeutic Strategies Targeting Iron Acquisition In Cmentioning
Iron acquisition is vital to microbial survival and is implicated in the virulence of many of the pathogens that reside in the cystic fibrosis (CF) lung. The multifaceted nature of iron acquisition by both bacterial and fungal pathogens encompasses a range of conserved and speciesspecific mechanisms, including secretion of iron-binding siderophores, utilization of siderophores from other species, release of iron from host iron-binding proteins and haemoproteins, and ferrous iron uptake. Pathogens adapt and deploy specific systems depending on iron availability, bioavailability of the iron pool, stage of infection and presence of competing pathogens. Understanding the dynamics of pathogen iron acquisition has the potential to unveil new avenues for therapeutic intervention to treat both acute and chronic CF infections. Here, we examine the range of strategies utilized by the primary CF pathogens to acquire iron and discuss the different approaches to targeting iron acquisition systems as an antimicrobial strategy.
“…This concept is based on the naturally occurring sideromycin antibiotics that mimic siderophores to gain intracellular access (Braun et al, 2009). Over the past three decades, numerous conjugates linking a siderophore or a siderophore mimic to different antibiotics via a linker molecule have been synthesized with varying degrees of antimicrobial efficacy (Möllmann et al, 2009;Wencewicz et al, 2009;Zeng et al, 2012;Fardeau et al, 2014). This approach, known as the 'Trojan horse' strategy, has been the subject of several reviews (including those by de Carvalho & Fernandes, 2014;Gó rska et al, 2014;Mislin & Schalk, 2014).…”
Section: Novel Therapeutic Strategies Targeting Iron Acquisition In Cmentioning
Iron acquisition is vital to microbial survival and is implicated in the virulence of many of the pathogens that reside in the cystic fibrosis (CF) lung. The multifaceted nature of iron acquisition by both bacterial and fungal pathogens encompasses a range of conserved and speciesspecific mechanisms, including secretion of iron-binding siderophores, utilization of siderophores from other species, release of iron from host iron-binding proteins and haemoproteins, and ferrous iron uptake. Pathogens adapt and deploy specific systems depending on iron availability, bioavailability of the iron pool, stage of infection and presence of competing pathogens. Understanding the dynamics of pathogen iron acquisition has the potential to unveil new avenues for therapeutic intervention to treat both acute and chronic CF infections. Here, we examine the range of strategies utilized by the primary CF pathogens to acquire iron and discuss the different approaches to targeting iron acquisition systems as an antimicrobial strategy.
“…59 siderophores or siderophore mimics. [78][79][80] Antibiotics from other classes, including ciprofloxacin, 81 spiramycin, 82 vancomycin, 83 norfloxacin, 84,85 and daptomycin 86,87 have also been conjugated with siderophores. Synthetic siderophore-ATB conjugates have been reported to enhance the uptake of the drugs, thus boosting and/or expanding the effectiveness of common ATBs.…”
Antimicrobial resistance has emerged as a huge challenge to the effective treatment of infectious diseases. Aside from a modest number of novel anti‐infective agents, very few new classes of antibiotics have been successfully developed for therapeutic use. Despite the research efforts of numerous scientists, the fight against antimicrobial (ATB) resistance has been a longstanding continued effort, as pathogens rapidly adapt and evolve through various strategies, to escape the action of ATBs. Among other mechanisms of resistance to antibiotics, the sophisticated envelopes surrounding microbes especially form a major barrier for almost all anti‐infective agents. In addition, the mammalian cell membrane presents another obstacle to the ATBs that target intracellular pathogens. To negotiate these biological membranes, scientists have developed drug delivery systems to help drugs traverse the cell wall; these are called “Trojan horse” strategies. Within these delivery systems, ATB molecules can be conjugated with one of many different types of carriers. These carriers could include any of the following: siderophores, antimicrobial peptides, cell‐penetrating peptides, antibodies, or even nanoparticles. In recent years, the Trojan horse‐inspired delivery systems have been increasingly reported as efficient strategies to expand the arsenal of therapeutic solutions and/or reinforce the effectiveness of conventional ATBs against drug‐resistant microbes, while also minimizing the side effects of these drugs. In this paper, we aim to review and report on the recent progress made in these newly prevalent ATB delivery strategies, within the current context of increasing ATB resistance.
“…This could be related to low solubility in aqueous media and/or the absence of hydrolysis of the hybrids. The hemolytic activity of the conjugates was low which indicated low cytotoxicity of obtained compounds [85]. Fig.…”
This review is aimed to provide extensive survey of quinolones and fluoroquinolones for a variety of applications ranging from metal complexes and nanoparticle development to hybrid conjugates with therapeutic uses. The review covers the literature from the past 10 years with emphasis placed on new applications and mechanisms of pharmacological action of quinolone derivatives. The following are considered: metal complexes, nanoparticles and nanodrugs, polymers, proteins and peptides, NO donors and analogs, anionic compounds, siderophores, phosphonates, and prodrugs with enhanced lipophilicity, phototherapeutics, fluorescent compounds, triazoles, hybrid drugs, bis-quinolones, and other modifications. This review provides a comprehensive resource, summarizing a broad range of important quinolone applications with great utility as a resource concerning both chemical modifications and also novel hybrid bifunctional therapeutic agents.Graphical abstract
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