Dioxoisoindolines have been included as a pharmacophore group in diverse drug-like molecules with a wide range of biological activity. Various reports have shown that phthalimide derivatives are potent inhibitors of AChE, a key enzyme involved in the deterioration of the cholinergic system during the development of Alzheimer’s disease. In the present study, 2-(2-(3,4-dimethoxyphenyl)ethyl)isoindoline-1,3-dione was synthesized, crystallized and evaluated as an AChE inhibitor. The geometric structure of the crystal and the theoretical compound (from molecular modeling) were analyzed and compared, finding a close correlation. The formation of the C6–H6···O19 interaction could be responsible for the non-negligible out of phenyl plane deviation of the C19 methoxy group, the O3 from the carbonyl group lead to C16–H16···O3 i intermolecular interactions to furnish C(9) and C(14) infinite chains within the (− 4 0 9) and (− 3 1 1) families of planes. Finally, the biological experiments reveal that the isoindoline-1,3-dione exerts a good competitive inhibition on AChE (Ki = 0.33–0.93 mM; 95% confidence interval) and has very low acute toxicity (LD 50 > 1600 mg/kg) compared to the AChE inhibitors currently approved for clinical use.
CITATION STYLE
Andrade-Jorge, E., Bribiesca-Carlos, J., Martínez-Martínez, F. J., Soriano-Ursúa, M. A., Padilla-Martínez, I. I., & Trujillo-Ferrara, J. G. (2018). Crystal structure, DFT calculations and evaluation of 2-(2-(3,4-dimethoxyphenyl) ethyl)isoindoline-1,3-dione as AChE inhibitor. Chemistry Central Journal, 12(1). https://doi.org/10.1186/s13065-018-0442-1
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