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Chem Biol Drug Des. 2017 Jan;89(1):141-151. doi: 10.1111/cbdd.12841. Epub 2016 Sep 26.

Rapid synthesis of flavone-based monoamine oxidase (MAO) inhibitors targeting two active sites using click chemistry.

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Institute of Bioengineering, Zhejiang University of Technology, Zhejiang, China.
Department of Chemistry, National University of Singapore, Singapore, Singapore.


A new library of flavone derivatives targeting two active sites of monoamine oxidases ("aromatic cage" and substrate cavity) were designed and synthesized using click chemistry (CuAAC reaction) between 6-N3 -2-phenyl chromones (Az1-Az2) and a series of alkynes (k1-k20). Their inhibitory activities against MAO isoforms (MAO-A and MAO-B) are evaluated. Compounds with fluorine, amide bonds, or amino bonds have shown better inhibition. The most potent flavone MAO inhibitor studied is Az2k19 (1.6 μm for MAO-A, 2.1 μm for MAO-B), while Az1k15 and Az2k15 displayed better selectivity toward MAO-B (SI > 10). Docking studies are in accordance with our hypothesis that these inhibitors are most likely located at both the substrate cavity and the "aromatic cage". Our results show that it is considerable to develop new MAO inhibitors from C6 substitution of flavone derivatives and that these compounds are also potential for the treatment of diseases associated with MAOs.


click chemistry; flavones; low cytotoxicity; molecular docking; monoamine oxidase inhibitors

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