Synthesis of model morpholine derivatives with biological activities by laccase-catalysed reactions.
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.
Hahn
Veronika
V
Institute of Microbiology, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany. veronikahahn@gmx.at
Mikolasch
Annett
A
Wende
Kristian
K
Bartrow
Hannelore
H
Lindequist
Ulrike
U
Schauer
Frieder
F
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001203:Ascomycota / Q000201:enzymology*; D001419:Bacteria / Q000187:drug effects; D002175:Candida / Q000187:drug effects; D002384:Catalysis; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005656:Fungal Proteins / Q000378:metabolism*; D006801:Humans; D042845:Laccase / Q000378:metabolism*; D015394:Molecular Structure; D009025:Morpholines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D000935:Antifungal Agents; D005656:Fungal Proteins; D009025:Morpholines; D042845:Laccase