Phenothiazine, anthraquinone and related tricyclic derivatives as inhibitors of d-amino acid oxidase

Abstract

A recent study has found that phenothiazine, anthraquinone and related tricyclic derivatives are good potency inhibitors of the monoamine oxidase (MAO) enzymes. Based on these findings, the present study investigated the possibility that these compounds may also inhibit another oxidase enzyme, d-amino acid oxidase (DAAO). The results show that seven of the study compounds exhibit good potency inhibition of DAAO with IC50 values that range from 0.309 to 6.27 µM. These values are comparable to that of the reference DAAO inhibitor, 3-methylpyrazole-5-carboxylic acid (IC50 = 1.34 µM). The most potent inhibitors are 2-chloro-7-methoxy-10H-phenothiazine (IC50 = 0.309 µM), 2-chlorophenothiazine (IC50 = 0.332 µM) and quinizarin (IC50 = 0.367 µM). It may be concluded that active DAAO inhibitors may serve as novel lead compounds for the design of DAAO inhibitors, compounds that may find future application in the treatment of neuropsychiatric disorders such as schizophrenia.

Keywords

• Phenothiazine
• Anthraquinone
• Tricyclic
• D-amino acid oxidase
• Inhibition