Synthesis of model morpholine derivatives with biological activities by laccase-catalysed reactions

Biotechnol Appl Biochem. 2009 Nov 13;54(4):187-95. doi: 10.1042/BA20090219.

Abstract

The efficient enzyme-catalysed reaction of morpholines as model structures for bioactive compounds with para-dihydroxylated aromatic systems was carried out using the oxidoreductase laccase and atmospheric oxygen to produce eight novel morpholine-substituted aromatics. The laccase of Myceliophthora thermophila was used for cross-linking morpholines containing primary or secondary amino groups with para-dihydroxylated laccase substrates. We demonstrate that not only primary amino groups, but also secondary amino groups, are able to couple with para-dihydroxylated aromatic systems in laccase-catalysed reactions. The resulting model products (yields up to 80%) were isolated, structurally characterized and tested for their antibacterial, antifungal and cytotoxic activities. Four of the eight products showed low to moderate growth inhibition against several Gram-positive and -negative bacterial strains and against the yeasts Candida maltosa and Candida albicans. The antibacterial and antifungal activities were determined by an agar disc diffusion test and a modified method according to the EUCAST discussion document E.Dis 7.1 [Rodríguez-Tudela et al. (2003) Clin. Microbiol. Infect. 9, i-viii] for the evaluation of MIC (minimal inhibitory concentration). Differences in cytotoxicity against the human urinary bladder carcinoma cell line 5637 are discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Anti-Infective Agents / chemical synthesis*
  • Anti-Infective Agents / chemistry
  • Anti-Infective Agents / pharmacology*
  • Antifungal Agents / chemical synthesis
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology
  • Ascomycota / enzymology*
  • Bacteria / drug effects
  • Candida / drug effects
  • Catalysis
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Fungal Proteins / metabolism*
  • Humans
  • Laccase / metabolism*
  • Molecular Structure
  • Morpholines / chemical synthesis*
  • Morpholines / chemistry
  • Morpholines / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Anti-Infective Agents
  • Antifungal Agents
  • Fungal Proteins
  • Morpholines
  • Laccase