Derivatization of the azole 1-aminobenzotriazole using laccase of Pycnoporus cinnabarinus and Myceliophthora thermophila: influence of methanol on the reaction and biological evaluation of the derivatives.
The laccases of Pycnoporus cinnabarinus and Myceliophthora thermophila are extracellular enzymes with high protein stability. They were used for the 'one pot' synthesis of azole derivatives from 1-aminobenzotriazole together with the p-dihydroxylated laccase substrates 2,5-dihydroxybenzoic acid methyl ester and 2,5-dihydroxybenzoic acid ethyl ester. The reactions yielded heteromolecular dimers (in yields of up to 34%). Methanol was used as the co-solvent to determine the influence of solvent concentration on the course of reaction. The resulting products were isolated, structurally characterized and tested for their antibacterial, antifungal and cytotoxic activities. The products showed low antimicrobial activity and low cytotoxicity compared with commercial available standard compounds but these variables exceeded those of the initial reactants used for the synthesis. In addition to the synthesis of heteromolecular dimers, oligomers were formed and structurally characterized by LC/MS (liquid chromatography/MS).
Hahn
Veronika
V
Institute of Microbiology, Ernst-Moritz-Arndt-University Greifswald, F.-L.-Jahnstr. 15, 17487 Greifswald, Germany. veronikahahn@gmx.at
Mikolasch
Annett
A
Wende
Kristian
K
Bartrow
Hannelore
H
Lindequist
Ulrike
U
Schauer
Frieder
F
D001412:Bacillus subtilis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005841:Gentisates / Q000737:chemistry; D006801:Humans; D042845:Laccase / Q000737:chemistry* / Q000378:metabolism; D000432:Methanol / Q000737:chemistry* / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D003904:Mitosporic Fungi / Q000201:enzymology*; D055494:Pycnoporus / Q000201:enzymology*; D013211:Staphylococcus aureus / Q000187:drug effects; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*
D005841:Gentisates; D014230:Triazoles; C033020:1-aminobenzotriazole; D042845:Laccase; D000432:Methanol