Trimethoxycinnamates and Their Cholinesterase Inhibitory Activity

0543720 - ÚVGZ 2022 RIV CH eng J - Journal Article
Kos, J. - Strharsky, T. - Štěpánková, Š. - Svrčková, K. - Oravec, Michal - Hošek, J. - Imramovský, A. - Jampílek, J.
Trimethoxycinnamates and Their Cholinesterase Inhibitory Activity.
Applied Sciences-Basel. Roč. 11, č. 10 (2021), č. článku 4691. E-ISSN 2076-3417
R&D Projects: GA MŠMT(CZ) EF16_019/0000797; GA MŠMT(CZ) LM2015061
Research Infrastructure: CzeCOS III - 90123
Institutional support: RVO:86652079
Keywords : biological evaluation * 3,4,5-trimethoxycinnamic acid * butyrylcholinesterase * acetylcholinesterase * derivatives * design * discovery * analogs * hybrids * trimethoxycinnamates * cholinesterase-inhibiting activity * cytotoxicity * structure-activity relationships
OECD category: Organic chemistry
Impact factor: 2.838, year: 2021
Method of publishing: Open access
https://www.mdpi.com/2076-3417/11/10/4691

A series of twelve nature-inspired 3,4,5-trimethoxycinnamates were prepared and characterized. All compounds, including the starting 3,4,5-trimethoxycinnamic acid, were tested for their ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in vitro, the selectivity index (SI) was also determined. 2-Fluororophenyl (2E)-3-(3,4,5-trimethoxyphenyl)-prop-2-enoate demonstrated the highest SI (1.71) in favor of BChE inhibition. 2-Chlorophenyl (2E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoate showed the highest AChE-inhibiting (IC50 = 46.18 mu M) as well as BChE-inhibiting (IC50 = 32.46 mu M) activity with an SI of 1.42. The mechanism of action of the most potent compound was determined by the Lineweaver-Burk plot as a mixed type of inhibition. An in vitro cell viability assay confirmed the insignificant cytotoxicity of the discussed compounds on the two cell lines. Trends between structure, physicochemical properties and activity were discussed.
Permanent Link: http://hdl.handle.net/11104/0320889