Steroid–Au^I–NHC Complexes: Synthesis and Antibacterial Activity

Abstract

A series of gold(I) pioneer complexes bearing N‐heterocyclic carbenes and steroid derivatives (ethynylestradiol and ethisterone) with the generic formula [Au(R2‐imidazol‐2‐ylidene)(steroid)] (where R=CH3 or CH2CH2OCH3) were synthesized, and the X‐ray structure of a rare of gold(I)–estradiol derivative is discussed. Toxicity studies reveal notable antibacterial activity of the gold‐based compounds, which is significantly increased in vivo by the presence of the estradiol unit. Toxicity profiling was estimated in vitro versus Gram‐positive (Staphylococcus aureus) and Gram‐negative (Escherichia coli) bacteria, and in vivo on Galleria mellonella larvae against E. coli.

Evaluation of in vitro and in vivo antibacterial activity of novel Cu(II)-steroid complexes

“…In this experiment complexes 8 and 9 induced 100% survival of larvae at 24 h and 80% at 48 h. DPPN derivatives 8 and 9 show very high in vivo activity only at higher concentration (0.25 mg/ml) while the DPPZ analogues 6 and 7 show the opposite behaviour (more active at lower concentration). The in vivo antimicrobial activity of the complexes does not strongly correlate with what was seen in vitro but this is quite common since the conditions in vivo are much different from those in vitro; the same lack of correlation was recently observed by our group with Au(I) complexes [17]. The role of the steroids and of the planar ligands in the activity of this series of Cu(II) complexes is not completely clear; the enhanced lipophlicity due to presence of the steroids that increase the bacterial uptake could explain in part the high antimicrobial activity but other mechanisms can be involved.…”

“…Recent results from our group showed that the presence of steroids (Estradiol and Testosterone) enhanced the in vivo antibacterial activity of Au(I)-NHC carbene complexes [17]. Since Copper and in particular Cu(II)-phenanthroline complexes are important antibacterial agents, we sought to combine these with steroid derivatives to confirm the efficacy of this approach.…”

“…[6][7][8][9][10][11][12] The free estradiol and testosterone were non-active as previously reported by us. [17] Among the series, the testosterone derivatives and DPQ, respectively). Two important factors are important: lipophilicity and solubility.…”

“…Considering these aspects, here we report the syntheses, characterization and antimicrobial evaluation of a series of Cu(II) complexes with chelating planar ligands further functionalised with steroids (testosterone and estradiol). We recently showed that the modification of Au(I)-NHC (N-Heterocyclic Carbenes) with steroids derivatives is a promising strategy to enhance the antibacterial activity of the related complexes [17]. In the work presented here the Cu(II) cationic complexes were evaluated as antibacterial agents in vitro against S. aureus and MRSA and in vivo using Galleria mellonella larvae.…”

Galleria mellonella as a consolidated in vivo model hosts: New developments in antibacterial strategies and novel drug testing

“…Both carbene precursors and complexes containing the oestradiol had antibacterial activity in vitro against E.coli and S. aureus, but in vivo tests with G. mellonella showed conflicting results. All the complexes tested showed no toxicity and the larvae infected with E. coli and treated with the compound containing oestradiol demonstrated increased survival, while the carbene precursors did not show any significant increase in larval survival even if in vitro studies demonstrated their antibacterial activity [86].…”