2-Heteroarylidene-1-indanone derivatives as inhibitors of monoamine oxidase |
| |
| Institution: | 1. Pharmaceutical Chemistry, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa;2. Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa;1. VTT Technical Research Centre of Finland, P.O. Box 1000, 02044 VTT, Finland;2. Skandinavisk Kemiinformation AB, Birkagatan 35, 11339 Stockholm, Sweden;3. Pöyry Management Consulting Oy, Jaakonkatu 3, 01620 Vantaa, Finland;4. Roal Oy, Tykkimäentie 15, 05200 Rajamäki, Finland;1. CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Kukrail Picnic Spot Road, P.O. CIMAP, Lucknow 226015, India;2. CSIR-Indian Institute of Integrative Medicine (CSIR-IIIM), Canal Road, Jammu 180001, India;3. CSIR-Central Drug Research Institute (CSIR-CDRI), B.S. 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India;1. Department of Chemistry, Institute of Chemical Sciences, Government College University, Lahore, Pakistan;2. Department of Chemistry, School of Physical and Chemical Sciences, Queen Mary University of London, London, United Kingdom;6. Department of Biotechnology, Savitribai Phule Pune University, Pune 411007, India |
| |
| Abstract: | 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 μM. Although with lower potencies, the derivatives also inhibit the MAO-A isoform with IC50 values as low as 0.061 μM. 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 ≈ 2-thiophene > cyclohexyl > 3-pyridine ≈ 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. |
| |
| Keywords: | Indanone Monoamine oxidase MAO Inhibition Chalcone SAR Heterocyclic |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
