Multifunctional Silver(I) Complexes with Metronidazole Drug Reveal Antimicrobial Properties and Antitumor Activity against Human Hepatoma and Colorectal Adenocarcinoma Cells

Cancers

Dominik Żyro¹  Justyn Ochocki¹  Agnieszka Śliwińska²  Izabela Korona-Głowniak³  Lidia Radko⁴  Andrzej Posyniak⁴  Lilianna Chęcińska⁵  Michał Wójcik⁶  Agata Przekora⁶  Joachim Kusz⁷ 

[1] Department of Bioinorganic Chemistry, Medical University of Lodz, Muszyńskiego 1, 90-151 Łódź, Poland;Department of Nucleic Acids Biochemistry, Medical University of Łódź, Pomorska 251, 92-213 Łódź, Poland;Department of Pharmaceutical Microbiology, Medical University of Lublin, Chodźki 1, 20-093 Lublin, Poland;Department of Pharmacology and Toxicology, National Veterinary Research Institute, Al. Partyzantów 57, 24-100 Puławy, Poland;Faculty of Chemistry, University of Lodz, Pomorska 163/165, 90-236 Łódź, Poland;Independent Unit of Tissue Engineering and Regenerative Medicine, Medical University of Lublin, Chodźki 1, 20-093 Lublin, Poland;Institute of Physics, University of Silesia, 75 Pułku Piechoty 1, 41-500 Chorzów, Poland;

关键词: cytotoxicity;    antimicrobial activity;    silver(I) complexes;    synthesis of silver(I) complexes;    light stability;    HepG2 cells;   

DOI  :  10.3390/cancers14040900

来源: DOAJ

【 摘 要 】

Silver salts and azole derivatives are well known for their antimicrobial properties. Recent evidence has demonstrated also their cytotoxic and genotoxic potential toward both normal and cancer cells. Still, little is known about the action of complexes of azoles with silver(I) salts. Thus, the goal of the study was to compare the chemical, cytotoxic and antimicrobial properties of metronidazole complexes with silver(I) nitrate and silver(I) sulfate to metronidazole and pure silver(I) salts. We synthetized a novel complex, [Ag(MTZ)₂]₂SO₄, and confirmed its chemical structure and properties using ¹H and ¹³C NMR spectroscopy and X-Ray, IR and elemental analysis. To establish the stability of complexes [Ag(MTZ)₂NO₃] and [Ag(MTZ)₂]₂SO₄, they were exposed to daylight and UV-A rays and were visually assessed. Their cytotoxicity toward human cancer cells (HepG2, Caco-2) and mice normal fibroblasts (Balb/c 3T3 clone A31) was determined by MTT, NRU, TPC and LDH assays. The micro-dilution broth method was used to evaluate their antimicrobial properties against Gram-positive and Gram-negative bacteria. A biofilm eradication study was also performed using the crystal violet method and confocal laser scanning microscopy. The photo-stability of the complexes was higher than silver(I) salts. In human cancer cells, [Ag(MTZ)₂]₂SO₄ was more cytotoxic than Ag₂SO₄ and, in turn, AgNO₃ was more cytotoxic than [Ag(MTZ)₂NO₃]. For Balb/c 3T3 cells, Ag₂SO₄ was more cytotoxic than [Ag(MTZ)₂]₂SO₄, while the cytotoxicity of AgNO₃ and [Ag(MTZ)₂NO₃] was similar. Metronidazole in the tested concentration range was non-cytotoxic for both normal and cancer cells. The complexes showed increased bioactivity against aerobic and facultative anaerobic bacteria when compared to metronidazole. For the majority of the tested bacterial strains, the silver(I) salts and complexes showed a higher antibacterial activity than MTZ; however, some bacterial strains presented the reverse effect. Our results showed that silver(I) complexes present higher photo-stability, cytotoxicity and antimicrobial activity in comparison to MTZ and, to a certain extent, to silver(I) salts.

【 授权许可】

Unknown