Bio‐Organometallic Derivatives of Antibacterial Drugs

Abstract

Overuse and misuse of antibacterial drugs has resulted in bacteria resistance and in an increase in mortality rates due to bacterial infections. Therefore, there is an imperative necessity of new antibacterial drugs. Bio-organometallic derivatives of antibacterial agents offer an opportunity to discover new active antibacterial drugs. These compounds are well-characterized products and, in several examples, their antibacterial activities have been studied. Both inhibition of the antibacterial activity and strong increase in the antibiotic activity of the parent drug have been found. The synthesis of the main classes of bio-organometallic derivatives of these drugs, as well as examples of the use of structure-activity relation&&Ok?&& (SAR) studies to increase the activity and to understand the mode of action of bio-organometallic antimicrobial peptides (BOAMPs) and platensimicyn bio-organometallic mimics is presented in this article.

Metal Complexes, an Untapped Source of Antibiotic Potential?

“…It is evident that the tip of the iceberg has only barely been scratched when it comes to investigating the antimicrobial potential of metal complexes (Table 2). Although there have been in vitro studies into many other elements, including chromium [115], iron [116], manganese [117][118][119][120], copper [121], rhodium [122], palladium [123,124], and platinum [125], these were often preliminary in nature and require further validation [27,124,126]. While some metal complexes and metal ions have been shown to possess excellent antimicrobial activity, the question remains whether or not metals offer any significant advantages over purely organic compounds.…”

“…In general, the article will restrict itself to studies into metal complexes, i.e., compounds where the metal ion is more or less stably coordinated by one or multiple ligands. A recent review provides an overview of organometallic derivatives of known antibacterial drugs [27]. While some overlaps exist, this work focuses on all metal-containing small molecules and includes many important reports that were published in 2019.…”

“…Almost 300 clinical trials featuring silver-containing compounds and formulations for a range of different applications are currently ongoing or in the recruitment phase [17]. Silver sulfadiazine is approved by the Food and Drug Administration (FDA) in the US for its use as a broad spectrum topical antibiotic for some burn wounds [27,31]. However, some trials have suggested that silver-based medicines generally do not perform better than non-silver-based treatments.…”

“…Finally, a 2019 meta-analysis of 81 studies found that 11/11 studies that met the inclusion criteria of the review found silver sulfadiazine to be inferior to alternative treatments in the mean wound-healing time [34].In the last 20 years, some new classes of silver complexes have garnered attention for their antibacterial properties, in particular N-heterocyclic carbene (NHC) complexes of silver(I). A comprehensive summary of antimicrobial silver compounds can be found in several recent reviews [27,[35][36][37]. While some complexes from the late 1990s and early 2000s showed promising activity against a range of bacterial strains, no significant developments have been reported in the last years, possibly due to the fact that the exact mode of action of silver compounds remained largely unknown.…”

Antibacterial effect of silver nanorings

“…To analyze the effect that conditioning through the presence of AgNPs might have on bacterial viability, aliquots of deionized water or BHI were kept in contact with nanostructures at different concentrations (10 10 , 2 x 10 10 , 4 x 10 10 , 8 x 10 10 , 16 x 10 10 Units/l) for a variable time (5,10,20,30,60 or 120 minutes, depending on the experiment) with stirring. Next, the AgNPs were removed by centrifugation at 3000 rpm for 5 minutes, and E. coli was incubated in the conditioned media at an A 600 of 0.5 for 30 minutes with stirring.…”