Hydroxy- or Methoxy-Substituted Benzaldoximes and Benzaldehyde- O-alkyloximes as Tyrosinase Inhibitors

• Published in: Bioorganic & medicinal chemistry 2001-07, Vol.9 (7), p.1879-1885
• Main Authors: Ley, Jakob P, Bertram, Heinz-Jürgen
• Format: Article
• Language: English
• Subjects: Analytical, structural and metabolic biochemistry; Biological and medical sciences; Enzyme Inhibitors - pharmacology; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Magnetic Resonance Spectroscopy; Mass Spectrometry; Monophenol Monooxygenase - antagonists & inhibitors; Oxidoreductases; Oximes - chemistry; Oximes - pharmacology
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/S0968-0896(01)00084-0

Several benzaldoximes, benzaldehyde- O-ethyloximes, and acetophenonoximes were synthesized and evaluated as tyrosinase inhibitors by an assay based on tyrosinase catalyzed L-DOPA oxidation. Whereas benzaldoxime itself is only a weak inhibitor, its derivatives with one or two hydroxy or methoxy moieties in para and meta positions depress tyrosinase activity. Acetophenonoximes and trisubstituted benzaldoximes show no inhibitory activity. The IC 50 of 3,4-dihydroxybenzaldehyde- O-ethyloxime (0.3 ± 0.1 μmol L −1) is of the same magnitude as tropolone (0.13 ± 0.08 μmol L −1), one of the best tyrosinase inhibitors known so far. Several benzaldoximes, benzaldehyde- O-ethyloximes, and acetophenone-oximes were synthesized and evaluated as tyrosinase inhibitors. The IC 50 of 3,4-dihydroxybenzaldehyde- O-ethyloxime (0.3±0.1 μmol L −1) is of the same magnitude as tropolone (0.13±0.08 μmol L −1), one of the best tyrosinase inhibitors known so far.