Tetrameric and polymeric silver complexes of the omeprazole scaffold; synthesis, structure, in vitro and in vivo antimicrobial activities and DNA interaction

Two complexes [AgI(pmtbH)]4 (1) and {[Ag4(pmtbH)4(NO3)4·2X}n (2) (where pmtbH is 2-[(2-pyridinylmethyl)thio]-1H-benzimidazole and X is H2O or MeOH) were synthesised and structurally characterised. Complex 2 showed therapeutic potential against Candida albicans, Escherichia coli, Staphylococcus aureu...

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Veröffentlicht in:Journal of inorganic biochemistry 2018-09, Vol.186, p.317-328
Hauptverfasser: Jakobsen, Vibe, Viganor, Livia, Blanco-Fernández, Alfonso, Howe, Orla, Devereux, Michael, McKenzie, Christine J., McKee, Vickie
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Sprache:eng
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Zusammenfassung:Two complexes [AgI(pmtbH)]4 (1) and {[Ag4(pmtbH)4(NO3)4·2X}n (2) (where pmtbH is 2-[(2-pyridinylmethyl)thio]-1H-benzimidazole and X is H2O or MeOH) were synthesised and structurally characterised. Complex 2 showed therapeutic potential against Candida albicans, Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa but complex 1 did not show significant activity in vitro. Further in vivo studies using larvae of the insect Galleria mellonella indicated that complex 2 significantly stimulates the immune system and that pre-treatment with the complex offers appreciable protection against all three bacteria. Real-time flow cytometry data support the observed antimicrobial profile of complex 2 and suggest the antimicrobial response may be linked to a form of bacterial programmed cell death (PCD). Complex 2 was found to interact with DNA in the bacterial and fungal cells but it did not cleave plasmid DNA isolated from the three bacteria. Silver complexes [AgI(pmtbH)]4 (1) and {[Ag4(pmtbH)4(NO3)4·2X}n (2) (pmtbH, 2-[(2-pyridinylmethyl)thio]-1H-benzimidazole; X, solvent) were structurally characterised. Complex 2 showed antimicrobial activity in vitro; and stimulates the immune system of Galleria mellonella larvae in vivo. Preliminary mechanistic studies using flow cytometry suggest the antimicrobial response is linked to bacterial programmed cell death. [Display omitted] •A polymeric silver complex shows antibacterial and antifungal activity.•Pre-treatment of larvae stimulates the immune system giving antibacterial protection.•The antimicrobial response can be linked to bacterial programmed cell death.
ISSN:0162-0134
1873-3344
DOI:10.1016/j.jinorgbio.2018.05.018