Antibacterial profiling of abietane-type diterpenoids

Bioorg Med Chem. 2017 Jan 1;25(1):132-137. doi: 10.1016/j.bmc.2016.10.019. Epub 2016 Oct 17.

Abstract

Abietic and dehydroabietic acid are interesting diterpenes with a highly diverse repertoire of associated bioactivities. They have, among others, shown antibacterial and antifungal activity, potentially valuable in the struggle against the increasing antimicrobial resistance and imminent antibiotic shortage. In this paper, we describe the synthesis of a set of 9 abietic and dehydroabietic acid derivatives containing amino acid side chains and their in vitro antimicrobial profiling against a panel of human pathogenic microbial strains. Furthermore, their in vitro cytotoxicity against mammalian cells was evaluated. The experimental results showed that the most promising compound was 10 [methyl N-(abiet-8,11,13-trien-18-yl)-d-serinate], with an MIC90 of 60μg/mL against Staphylococcus aureus ATCC 25923, and 8μg/mL against methicillin-resistant S. aureus, Staphylococcus epidermidis and Streptococcus mitis. The IC50 value for compound 10 against Balb/c 3T3 cells was 45μg/mL.

Keywords: Abietic acid; Amino acid derivative; Bacteria; Cytotoxicity; Dehydroabietic acid; Fungi.

MeSH terms

  • Abietanes / chemistry*
  • Abietanes / pharmacology*
  • Animals
  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology*
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology
  • BALB 3T3 Cells
  • Bacteria / drug effects
  • Bacterial Infections / drug therapy
  • Fungi / drug effects
  • Humans
  • Methicillin-Resistant Staphylococcus aureus / drug effects
  • Mice
  • Microbial Sensitivity Tests
  • Mycoses / drug therapy
  • Staphylococcus aureus / drug effects
  • Staphylococcus epidermidis / drug effects

Substances

  • Abietanes
  • Anti-Bacterial Agents
  • Antifungal Agents
  • dehydroabietic acid
  • abietic acid