Investigation of the monoamine oxidase inhibition properties of benzoxathiolone derivatives

被引:1
|
作者
Prinsloo, Izak F. [1 ]
Petzer, Anel [1 ]
Cloete, Theunis T. [1 ]
Petzer, Jacobus P. [1 ]
机构
[1] North West Univ, Ctr Excellence Pharmaceut Sci, Sch Pharm, Pharmaceut Chem, ZA-2520 Potchefstroom, South Africa
基金
新加坡国家研究基金会;
关键词
Tioxolone; Benzoxathiolone; Neurodegenerative disorder; Enzyme inhibition; Monoamine oxidase; MAO; REVERSIBLE INHIBITORS;
D O I
10.1007/s00044-023-03042-w
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
The treatment of neuropsychiatric and neurodegenerative disorders such as depression and Parkinson's disease represent significant challenges in healthcare. Enzymes that metabolise neurotransmitter amines are important drug targets for these disorders and inhibitors of these enzymes have played key roles as therapeutic agents. For example, inhibitors of monoamine oxidase (MAO) A have been used for decades as antidepressant agents and act by inhibiting the central metabolism of serotonin and noradrenaline, while MAO-B inhibitors conserve central dopamine supply and have been used to treat Parkinson's disease. Literature reports that benzoxathiolone derivatives act as potent MAO inhibitors with specificity for the MAO-B isoform. To expand on these findings, the present study synthesised series of benzoxathiolone derivatives and investigated their human MAO inhibition properties. The results showed that the benzoxathiolone derivatives were potent MAO inhibitors, with the most potent compounds exhibiting IC50 values of 0.083 and 0.086 mu M (4d and 5e) and 0.0069 and 0.0066 mu M (3a and 3b) for MAO-A and MAO-B, respectively. Compounds 4d and 5e are significantly more potent MAO-A inhibitors compared to those reported previously. It may be concluded that benzoxathiolone derived compounds may act as future leads for the development of new treatments for depression and Parkinson's disease. [Graphics] .
引用
收藏
页码:827 / 840
页数:14
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