New antibacterial, non-genotoxic materials, derived from the functionalization of the anti-thyroid drug methimazole with silver ions

• Published in: Journal of inorganic biochemistry 2016-07, Vol.160, p.114-124
• Main Authors: Sainis, I., Banti, C.N., Owczarzak, A.M., Kyros, L., Kourkoumelis, N., Kubicki, M., Hadjikakou, S.K.
• Format: Article
• Language: English
• Subjects: Allium cepa; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - pharmacology; Antithyroid Agents - chemical synthesis; Antithyroid Agents - pharmacology; Binding Sites; Coordination Complexes - chemical synthesis; Coordination Complexes - pharmacology; CT-DNA; DNA - chemistry; Drug Repositioning; Escherichia coli; Escherichia coli - drug effects; Escherichia coli - growth & development; Genotoxicity; Hydrogen Bonding; Methimazole; Methimazole - chemical synthesis; Methimazole - pharmacology; Microbial Sensitivity Tests; Mitotic Index; Molecular Docking Simulation; Onions - cytology; Onions - drug effects; Onions - genetics; Organophosphorus Compounds - chemistry; Pseudomonas aeruginosa; Pseudomonas aeruginosa - drug effects; Pseudomonas aeruginosa - growth & development; Pseudomonas aeruginosa and Escherichia coli; Silver - chemistry; Silver Nitrate - pharmacology; Silver(I) compounds; Toluene - chemistry
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2015.12.013

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), 1H, 31P-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. Mixed ligand silver(I) complexes of the antithyroid drug methimazole (MMI): {[AgBr(μ2-S-MMI)(TPP))]2} (1) and [AgCl(TPP)2(MMI)] (2) (TPP=triphenylphosphine, were evaluated for their antibacterial effect against the bacterial species Pseudomonas aeruginosa (PAO) and Escherichia coli (E. coli). The in vivo genotoxicity of 1–2 was evaluated by Allium cepa test. [Display omitted] •Synthesis and characterization of silver(I) complexes•Antimicrobial activity of silver complexes and their interaction with CT-DNA•The steric effect of arylphosphines towards the antimicrobial activity of the complexes•Genotoxicity