Monoamine oxidase (MAO) is an important drug target as the MAO isoforms play key roles in neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease, as well as in neuropsychiatric diseases such as depression. Methylene blue is an inhibitor of MAO-A, while azure B, the major metabolite of methylene blue, and various other structural analogues retain the ability to inhibit MAO-A. Based on this, the present study evaluated 22 dyes, many of which are structurally related to methylene blue, as potential inhibitors of human MAO-A and MAO-B. The results highlighted three dye compounds as good potency competitive and reversible MAO inhibitors, and which exhibit higher MAO inhibition than methylene blue: acridine orange, oxazine 170 and Darrow red. Acridine orange was found to be a MAO-A specific inhibitor (IC50 = 0.017 μM), whereas oxazine 170 is a MAO-B specific inhibitor (IC50 = 0.0065 μM). Darrow red was found to be a non-specific MAO inhibitor (MAO-A, IC50 = 0.059 μM; MAO-B, IC50 = 0.065 μM). These compounds may be advanced for further testing and preclinical development, or be used as possible lead compounds for the future design of MAO inhibitors.
Keywords: Darrow red; acridine orange; inhibition; methylene blue; monoamine oxidase; oxazine 170.
© 2019 John Wiley & Sons A/S.