title: New antibacterial, non-genotoxic materials, derived from the functionalization of the anti-thyroid drug methimazole with silver ions.
abstract: The new silver(I) compound {[AgBr(μ2-S-MMI)(TPP))]2} (1) and the known one [AgCl(TPP)2(MMI)] (2) were obtained by refluxing toluene solutions of silver(I) halide with triphenylphosphine (TPP) and the anti-thyroid drug 2-mercapto-1-methyl-imidazole or methimazole (MMI). The complexes were characterized by m.p., vibrational spectroscopy (mid-FT-IR), (1)H, (31)P-NMR, UV-Vis spectroscopic techniques and X-ray crystallography. The antibacterial effect of 1 and 2 against the bacterial species Pseudomonas aeruginosa (PAO) and Escherichia coli was evaluated. Compound 1 exhibits comparable activity to the corresponding one of the silver nitrate which is an antibacterial drug in use. The in vivo genotoxicity of 1-2 by the mean of Allium cepa test shows no alterations in the mitotic index values due to the absence of chromosomal aberrations. The mechanism of action of the title compounds is evaluated. The DNA binding tests indicate the ability of the complexes 1-2 to modify the activity of the bacteria. The binding constants of 1-2 towards CT-DNA indicate interaction through opening of the hydrogen bonds of DNA. Docking studies on DNA-complexes interactions confirm the binding of both complexes 1-2 in the major groove of the CT-DNA. In conclusion the silver complex 1 is an anti-bacterial and non-genotoxic material, which can be applied to antibacterial drug in the future.
authors.affiliation: Cancer Biobank Center, University of Ioannina, Greece.
authors.forename: I
authors.initials: I
authors.lastname: Sainis
authors.affiliation: Section of Inorganic and Analytical Chemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece. Electronic address: cbanti@cc.uoi.gr.
authors.forename: C N
authors.initials: CN
authors.lastname: Banti
authors.affiliation: Department of Chemistry, Adam Mickiewicz University, Umultowska 89b, 61-614 Poznań, Poland.
authors.forename: A M
authors.initials: AM
authors.lastname: Owczarzak
authors.affiliation: Section of Inorganic and Analytical Chemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece.
authors.forename: L
authors.initials: L
authors.lastname: Kyros
authors.affiliation: Medical Physics Laboratory, Medical School, University of Ioannina, Greece. Electronic address: nkourkou@uoi.gr.
authors.forename: N
authors.initials: N
authors.lastname: Kourkoumelis
authors.affiliation: Department of Chemistry, Adam Mickiewicz University, Umultowska 89b, 61-614 Poznań, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Kubicki
authors.affiliation: Section of Inorganic and Analytical Chemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece. Electronic address: shadjika@uoi.gr.
authors.forename: S K
authors.initials: SK
authors.lastname: Hadjikakou
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D013956:Antithyroid Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001665:Binding Sites; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000494:pharmacology; D004247:DNA / Q000737:chemistry; D058492:Drug Repositioning; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D006860:Hydrogen Bonding; D008713:Methimazole / Q000138:chemical synthesis* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008940:Mitotic Index; D062105:Molecular Docking Simulation; D019697:Onions / Q000166:cytology / Q000187:drug effects / Q000235:genetics; D009943:Organophosphorus Compounds / Q000737:chemistry; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000254:growth & development; D012834:Silver / Q000737:chemistry*; D012835:Silver Nitrate / Q000494:pharmacology; D014050:Toluene / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D013956:Antithyroid Agents; D056831:Coordination Complexes; D009943:Organophosphorus Compounds; C061896:triphenylphosphine; D014050:Toluene; D012834:Silver; D008713:Methimazole; D004247:DNA; C427203:calf thymus DNA; D012835:Silver Nitrate
keywords: CT-DNA; Genotoxicity; Methimazole; Pseudomonas aeruginosa and Escherichia coli; Silver(I) compounds