1-Hydroxynaphthalene-4-trifluoromethylphenyl chalcone and 3‑hydroxy-4-trifluoromethylphenyl flavone: A combined experimental, structural, in vitro AChE, BChE and in silico studies

• Published in: Journal of molecular structure 2022-04, Vol.1253, p.132253, Article 132253
• Main Authors: Ghias, Mehreen, Ahmed, Muhammad Naeem, Sajjad, Bakhtawar, Ibrahim, Mahmoud A.A., Rashid, Umer, Shah, Syed Wadood Ali, Shoaib, Mohammad, Madni, Murtaza, Tahir, Muhammad Nawaz, Macías, Mario A.
• Format: Article
• Language: English
• Subjects: AChe; BChe; Chalcone; Flavone; Hirshfeld surface maps; Molecular packing; Structural energy
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2021.132253

•in vitro AChE, BChE and in silico studies of chalcone and flavone compounds.•Crystallographic, Hirshfeld surface, and energy frameworks analyses were performed.•Binding to catalytic active site and mid-gorge residues of acetylcholinesterase.•Exist correlations between intra/inter-molecular hydrogen bonds. The synthesis, X-ray characterization, in vitro AChE, BChE and in silico studies of (E)-1-(1-hydroxynaphthalen-2-yl)-3-(4-(trifluoromethyl)phenyl)prop‑2-en-1-one (1) and 3‑hydroxy-2-(4-(trifluoromethyl)phenyl)-4H-chromen-4-one (2) are reported in this manuscript. Both compounds are obtained in good yield (64–70%). The crystal structures of 1, and 2 are affected by the strength of intramolecular O‒H‧‧‧O hydrogen bonds altering the proportion of electrostatic and dispersion forces participating in the solid. Moderate to good activities against AChE and BChE were shown by the target compounds in comparison to reference drug galantamine. Molecular modeling studies via docking simulations indicated that compounds showed binding to the catalytic active site and mid-gorge residues of acetylcholinesterase. [Display omitted]