Evaluation of a 2-aminoimidazole variant as adjuvant treatment for dermal bacterial infections

Drug Des Devel Ther. 2017 Jan 16:11:153-162. doi: 10.2147/DDDT.S111865. eCollection 2017.

Abstract

2-Aminoimidazole (2-AI)-based compounds have been shown to efficiently disrupt biofilm formation, disperse existing biofilms, and resensitize numerous multidrug-resistant bacteria to antibiotics. Using Pseudomonas aeruginosa and Staphylococcus aureus, we provide initial pharmacological studies regarding the application of a 2-AI as a topical adjuvant for persistent dermal infections. In vitro assays indicated that the 2-AI H10 is nonbactericidal, resensitizes bacteria to antibiotics, does not harm the integument, and promotes wound healing. Furthermore, in vivo application of H10 on swine skin caused no gross abnormalities or immune reactions. Taken together, these results indicate that H10 represents a promising lead dermal adjuvant compound.

Keywords: ESKAPE pathogens; antimicrobial activity; drip-flow reactor; oroidin derivative; skin irritation; synergism; transdermal absorption.

MeSH terms

  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use*
  • Biofilms / drug effects
  • Chemotherapy, Adjuvant
  • Dose-Response Relationship, Drug
  • Humans
  • Imidazoles / administration & dosage
  • Imidazoles / pharmacology
  • Imidazoles / therapeutic use*
  • Microbial Sensitivity Tests
  • Pseudomonas aeruginosa / drug effects
  • Pseudomonas aeruginosa / growth & development
  • Skin Diseases, Bacterial / drug therapy*
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / growth & development
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Imidazoles
  • 2-aminoimidazole