Pharmacological Evaluation of Novel Organoiron Dendrimers as Antimicrobial and Anti-Inflammatory Agents

Macromol Biosci. 2021 Jan;21(1):e2000242. doi: 10.1002/mabi.202000242. Epub 2020 Oct 15.

Abstract

The synthesis of a novel and attractive class of nonsteroidal anti-inflammatory and antimicrobial organoiron dendrimers attached to the well-known drug ibuprofen is achieved. The structures of these dendrimers are established by spectroscopic and analytical techniques. The antimicrobial activity of these dendrimers is investigated and tested against five human pathogenic Gram-positive and Gram-negative bacteria, and minimum inhibitory concentrations are reported. Some of these synthesized dendrimers exhibit higher inhibitory activity against methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, and Staphylococcus warneri compare to the reference drugs. As well, the in vitro and in vivo anti-inflammatory activities of these dendrimers are evaluated. The results of in vivo anti-inflammatory activity and histopathology of inflamed paws show that all dendrimers display considerable anti-inflammatory activity; however, second-generation dendrimer (G2-D6) shows the best anti-inflammatory activity, which is more potent than the commercial drug ibuprofen at the same tested dose. Results of the toxicity study reveal that G2-D6 is the safest drug on biological tissues.

Keywords: COX-2; dendrimer; ibuprofen; in vivo and in vitro anti-inflammatory activity; toxicity.

MeSH terms

  • Anti-Infective Agents / chemistry
  • Anti-Infective Agents / pharmacology
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology
  • Bacterial Infections / drug therapy*
  • Bacterial Infections / microbiology
  • Dendrimers / chemistry
  • Dendrimers / pharmacology*
  • Gram-Negative Bacteria / drug effects
  • Gram-Positive Bacteria / drug effects
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / microbiology
  • Microbial Sensitivity Tests
  • Organoiron Compounds / chemistry
  • Organoiron Compounds / pharmacology*
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / pathogenicity

Substances

  • Anti-Infective Agents
  • Anti-Inflammatory Agents
  • Dendrimers
  • Organoiron Compounds