Silver complex of salicylic acid and its hydrogel-cream in wound healing chemotherapy

J Inorg Biochem. 2018 Apr:181:41-55. doi: 10.1016/j.jinorgbio.2018.01.004. Epub 2018 Feb 3.

Abstract

The known metallotherapeutic [Ag(salH)]2 (AGSAL-1) of salicylic acid (salH2), was used for the development of new efficient silver based material for wounds healing. AGSAL-1 was characterized by spectroscopic techniques and X-ray crystallography. The wound healing epithelialization of AGSAL-1 was investigated by the means of scratch assay against immortalized human keratinocytes (HaCaT) cells. The anti-inflammatory activity of AGSAL-1 was evaluated by monitoring the catalytic peroxidation of linoleic acid to hydroperoxylinoleic acid by the enzyme lipoxygenase (LOX). The antibacterial activity of AGSAL-1 was evaluated against bacterial species which colonize wounds, such as: Pseudomonas aeruginosa (PAO1), Staphylococcus epidermidis and Staphylococcus aureus, by the means of Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC) and their Inhibition Zone (IZ). Moreover, the influence of AGSAL-1 against the formation of biofilm of PAO1 and St. aureus was also evaluated by the mean of Biofilm Elimination Concentration (ΒΕC). A hydrogel material CMC@AGSAL-1, based on the dispersion of AGSAL-1 in to carboxymethyl cellulose (CMC) was tested for its antimicrobial activity. Molecular Docking was performed, to explore the molecular interaction of AGSAL-1 with (i) the transcriptional regulator of PAO1, LasR. (ii) the mevalonate pathway for the biosynthesis of isoprenoids which is essential for gram-positive bacteria St. epidermidis and St. aureus. The toxicity of AGSAL-1 was examined against the HaCaT cells. Its genotoxicity was evaluated using Allium cepa model, in vivo. No genotoxicity was detected, indicating that AGSAL-1 is a candidate towards the development on a new efficient medication of the silver based metallodrugs.

Keywords: Anti-inflammatory; Antibacterial; Bioinorganic materials chemistry; Salicylic acid; Silver(I) complexes; Wound healing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / metabolism
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / metabolism
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism
  • Biofilms / drug effects
  • Cell Line
  • Coordination Complexes / adverse effects
  • Coordination Complexes / chemistry
  • Coordination Complexes / metabolism
  • Coordination Complexes / pharmacology*
  • Crystallography, X-Ray
  • Disk Diffusion Antimicrobial Tests
  • Humans
  • Hydrogels
  • Keratinocytes / cytology
  • Keratinocytes / drug effects*
  • Keratinocytes / immunology
  • Keratinocytes / metabolism
  • Ligands
  • Molecular Conformation
  • Molecular Docking Simulation
  • Mutagenicity Tests
  • Pseudomonas aeruginosa / drug effects
  • Pseudomonas aeruginosa / growth & development
  • Pseudomonas aeruginosa / physiology
  • Salicylic Acid / adverse effects
  • Salicylic Acid / chemistry
  • Salicylic Acid / metabolism
  • Salicylic Acid / pharmacology*
  • Silver / adverse effects
  • Silver / chemistry
  • Silver / metabolism
  • Silver / pharmacology*
  • Skin Cream
  • Staphylococcus / drug effects
  • Staphylococcus / growth & development
  • Staphylococcus / physiology
  • Trans-Activators / chemistry
  • Trans-Activators / metabolism
  • Wound Healing / drug effects*

Substances

  • Anti-Bacterial Agents
  • Anti-Inflammatory Agents, Non-Steroidal
  • Bacterial Proteins
  • Coordination Complexes
  • Hydrogels
  • Ligands
  • Trans-Activators
  • Silver
  • Salicylic Acid