The inhibition of monoamine oxidase by 2-methylbenzo[d]oxazole derivatives

The monoamine oxidase (MAO) enzymes metabolise neurotransmitter amines and are drug targets for the treatment of neuropsychiatric and neurodegenerative disorders. Over the past several decades, MAO inhibitors have been used as antidepressants and antiparkinsonian agents. The present study investigated the MAO inhibition properties of a series of benzoxazole derivatives. Many benzoxazole-containing drugs have been marketed and are used for the treatment of a wide variety of conditions. Thirteen 2-methylbenzo[d]oxazole derivatives (1a–f, 2a–g) were synthesised and evaluated as in vitro inhibitors of human MAO. The results showed that the benzoxazole derivatives were potent MAO inhibitors. Compounds 1d and 2e were the most potent MAO-B inhibitors with IC₅₀ values of 0.0023 and 0.0033 µM, respectively. The most potent MAO-A inhibition was displayed by compounds 2c and 2e with IC₅₀ values of 0.670 and 0.592 µM, respectively. It may be concluded that the benzoxazole derivatives of this study could be useful lead compounds for the development of clinically useful MAO inhibitors.