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Synthesis and in vitro study of new coumarin derivatives linked to nicotinonitrile moieties as potential acetylcholinesterase inhibitors
Author(s) -
Mekky Ahmed E. M.,
Sanad Sherif M. H.
Publication year - 2020
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.4134
Subject(s) - chemistry , coumarin , acetylcholinesterase , sodium azide , in vitro , stereochemistry , pyridine , ic50 , nuclear chemistry , combinatorial chemistry , organic chemistry , biochemistry , enzyme
The appropriate pyridine‐2(1 H )‐thiones were reacted with an equivalent amount of 5‐(chloromethyl)‐2‐hydroxybenzaldehyde in ethanol in the presence of potassium hydroxide to give the corresponding 2‐hydroxybenzaldehyde derivatives in excellent yields. The latter derivatives were taken as key synthons for the preparation of the target hybrids. Therefore, 2‐hydroxybenzaldehydes were reacted with benzoylglycine in acetic anhydride in the presence of fused sodium acetate at 100°C for 6 hours to afford a new series of nicotinonitrile‐coumarin hybrids. The in vitro acetylcholinesterase inhibitory activities were estimated for the new coumarins. The results were expressed as the inhibition percentage of the tested hybrids at concentration of 25 nM, compared to donepezil as a reference (inhibition percentage of 70.5). Coumarin hybrids linked to 6‐(4‐nitrophenyl) or 6‐(4‐chlorophenyl)‐4‐phenylnicotinonitrile exhibited more effective inhibitory activities than donepezil with inhibition percentages of 94.1 and 72.3, respectively. The new coumarins were tested for their free radical‐scavenging capabilities against DPPH. Furthermore, some new coumarins were tested for in vitro cytotoxic activity against each MCF‐10A, MCF‐7, Caco2, and HEPG2. The new hybrids showed cytotoxicity in micromolar range (IC 50 of 3.5‐13.9 μM) against all tested cell lines. These results clearly demonstrated that the hybrids being tested are not cytotoxic at the concentration required to inhibit acetylcholinesterase effectively.