Structure–activity relationship investigation of tertiary amine derivatives of cinnamic acid as acetylcholinesterase and butyrylcholinesterase inhibitors: compared with that of phenylpropionic acid, sorbic acid and hexanoic acid

<p>In the present investigation, 48 new tertiary amine derivatives of cinnamic acid, phenylpropionic acid, sorbic acid and hexanoic acid (<b>4d</b>–<b>6g</b>, <b>10d</b>–<b>12g</b>, <b>16d</b>–<b>18g</b> and <b>22d</b>–<b>24g</b>) were designed, synthesized and evaluated for the effect on AChE and BChE <i>in vitro</i>. The results revealed that the alteration of aminoalkyl types and substituted positions markedly influences the effects in inhibiting AChE. Almost of all cinnamic acid derivatives had the most potent inhibitory activity than that of other acid derivatives with the same aminoalkyl side chain. Unsaturated bond and benzene ring in cinnamic acid scaffold seems important for the inhibitory activity against AChE. Among them, compound <b>6g</b> revealed the most potent AChE inhibitory activity (IC₅₀ value: 3.64 µmol/L) and highest selectivity over BChE (ratio: 28.6). Enzyme kinetic study showed that it present a mixed-type inhibition against AChE. The molecular docking study suggested that it can bind with the catalytic site and peripheral site of AChE.</p

Fluorination Effects on the Shapes of Complexes of Water with Ethers: A Rotational Study of Trifluoroanisole–Water

The rotational spectra of five isotopologues of the 1:1 complex trifluoroanisole–water have been investigated with pulsed jet Fourier transform microwave spectroscopy. The triple fluorination of the methyl group greatly affects the features of the rotational spectrum of the complex with water, with respect to those of the related complex anisole–water. The shape, the internal dynamics, and the isotopic effects turned out to be quite different from those of the anisole–water adduct (Giuliano, B. M.; Caminati, W. Angew. Chem., Int. Ed. 2005, 44, 603−606). However, as in anisole–water, water has the double role as a proton donor and proton acceptor, and it is linked to trifluoroanisole through two, O–H···O and C–H···O hydrogen bonds

Structure–activity relationship investigation of benzamide and picolinamide derivatives containing dimethylamine side chain as acetylcholinesterase inhibitors

<p>A series of benzamide and picolinamide derivatives containing dimethylamine side chain (<b>4a</b>–<b>4c</b> and <b>7a</b>–<b>7i</b>) were synthesised and evaluated for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity <i>in vitro</i>. Structure–activity relationship investigation revealed that the substituted position of dimethylamine side chain markedly influenced the inhibitory activity and selectivity against AChE and BChE. In addition, it seemed that the bioactivity of picolinamide amide derivatives was stronger than that of benzamide derivatives. Among them, compound <b>7a</b> revealed the most potent AChE inhibitory activity (IC₅₀: 2.49 ± 0.19 μM) and the highest selectivity against AChE over BChE (Ratio: 99.40). Enzyme kinetic study indicated that compound <b>7a</b> show a mixed-type inhibition against AChE. The molecular docking study revealed that this compound can bind with both the catalytic site and the peripheral site of AChE.</p