Molecular Diversity p. 491 - 507 (2021)
Update date:2022-09-26
Topics:
Cloete, Stephanus J.
N’Da, Clarina I.
Legoabe, Lesetja J.
Petzer, Anél
Petzer, Jacobus P.
Abstract: Monoamine oxidase (MAO) is of much clinical relevance, and inhibitors of this enzyme are used in the treatment for neuropsychiatric and neurodegenerative disorders such as depression and Parkinson’s disease. The present study synthesises and evaluates the MAO inhibition properties of a series of 33 1-tetralone and 4-chromanone derivatives in an attempt to discover high-potency compounds and to expand on the structure–activity relationships of MAO inhibition by these classes. Among these series, eight submicromolar MAO-A inhibitors and 28 submicromolar MAO-B inhibitors are reported, with all compounds acting as specific inhibitors of the MAO-B isoform. The most potent inhibitor was a 1-tetralone derivative (1h) with IC50 values of 0.036 and 0.0011?μM for MAO-A and MAO-B, respectively. Interestingly, with the reduction of 1-tetralones to the corresponding alcohols, a decrease in MAO inhibition potency is observed. Among these 1-tetralol derivatives, 1p (IC50 = 0.785?μM) and 1o (IC50 = 0.0075?μM) were identified as particularly potent inhibitors of MAO-A and MAO-B, respectively. Potent compounds such as those reported here may act as leads for the future development of MAO-B specific inhibitors. Graphic abstract: The present study describes the MAO inhibitory activities of a series of 1-tetralone and 4-chromanone derivatives. Numerous high-potency MAO-B specific inhibitors were identified.[Figure not available: see fulltext.].
View Morewebsite:http://www.chemdow.com
Contact:0086-10-82435335
Address:Room 401,Unit 3,4th Floor,Shangdijiayuan,Shangdi East Road, Haidian District,Beijing
website:http://www.sagechem.com
Contact:+86-571-86818502
Address:Room C1301, New Youth Plaza, 8 Jia Shan Road, Hangzhou, China
Hangzhou innopharma technology Co,.Ltd.
Contact:+86-13388601988
Address:Room845,lixin building, moganshan road, hangzhou, china
website:http://www.sigmaaldrich.com
Contact:800 558-9160
Address:Industriestrasse 25CH-9471 Buchs SGSwitzerland
Jiangsu Feymer Technology Co., Ltd.
Contact:+86-512-58110622/58110118
Address:Fenghuang Town, Zhangjiagang City, Jiangsu Province, China
Doi:10.1039/a804412k
(1998)Doi:10.1007/BF00771657
()Doi:10.1007/BF00471253
()Doi:10.1007/BF00861482
()Doi:10.1021/jm00297a039
(1970)Doi:10.1016/S0040-4039(00)00252-5
(2000)