期刊
BIOORGANIC CHEMISTRY
卷 69, 期 -, 页码 20-28出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bioorg.2016.09.004
关键词
Indanone; Monoamine oxidase; MAO; Inhibition; Chalcone; SAR; Heterocyclic
资金
- Medical Research Council
- National Research Foundation of South Africa [85642, 96180, 96135]
- NRF
In the present study a series of fifteen 2-heteroarylidene-1-indanone derivatives were synthesised and evaluated as inhibitors of recombinant human monoamine oxidase (MAO) A and B. These compounds are structurally related to series of heterocyclic chalcone derivatives which have previously been shown to act as MAO-B specific inhibitors. The results document that the 2-heteroarylidene-1-indanones are in vitro inhibitors of MAO-B, displaying IC50 values of 0.0044-1.53 mu M. Although with lower potencies, the derivatives also inhibit the MAO-A isoform with IC50 values as low as 0.061 mu M. An analysis of the structure-activity relationships for MAO-B inhibition indicates that substitution with the methoxy group on the A-ring leads to a significant enhancement in MAO-B inhibition compared to the unsubstituted homologues while the effect of the heteroaromatic substituent on activity, in decreasing order is: 5-bromo-2-furan > 5-methyl-2-furan > 2-pyridine approximate to 2-thiophene > cyclohexyl > 3-pyridine approximate to 2-furan. It may therefore be concluded that 2-heteroarylidene-1-indanone derivatives are promising leads for the design of MAO inhibitors for the treatment of Parkinson's disease and possibly other neurodegenerative disorders. (C) 2016 Elsevier Inc. All rights reserved.
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