TY - JOUR
T1 - Crystal structure, DFT calculations and evaluation of 2-(2-(3,4-dimethoxyphenyl) ethyl)isoindoline-1,3-dione as AChE inhibitor
AU - Andrade-Jorge, Erik
AU - Bribiesca-Carlos, José
AU - Martínez-Martínez, Francisco J.
AU - Soriano-Ursúa, Marvin A.
AU - Padilla-Martínez, Itzia I.
AU - Trujillo-Ferrara, José G.
N1 - Publisher Copyright:
© The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
KW - 3-Dione
KW - AChE inhibitor
KW - Alzheimer’s disease
KW - Crystal structure
KW - Isoindoline-1
KW - Kinetic
UR - http://www.scopus.com/inward/record.url?scp=85051067153&partnerID=8YFLogxK
U2 - 10.1186/s13065-018-0442-1
DO - 10.1186/s13065-018-0442-1
M3 - Artículo
C2 - 29938351
AN - SCOPUS:85051067153
SN - 1752-153X
VL - 12
JO - Chemistry Central Journal
JF - Chemistry Central Journal
IS - 1
M1 - 74
ER -