In vitro anticholinesterase activities, molecular docking studies, DFT calculations and drug-likeness characters of β-keto ester

Keto esters have been reported to exhibit biological activities such as antitumor, antibacterial, and antifungal effects. In the current study, cholinesterase inhibitor potentials of beta-keto ester derivatives were evaluated by in vitro enzyme inhibition assays. Among the synthesized compounds, it was determined that while derivative 2l, dimethyl 2-(4-bromobenzoyl) succinate (IC50 of 1.21 mu M), showed a strong inhibition effect on acetylcholinesterase (AChE). Most effective molecule on butyrylcholinesterase (BuChE) was 2n, dimethyl 2-([1,1'-biphenyl]-4-carbonyl)succinate, having IC50 as 26.54 mu M. The free binding energies of ligands were estimated between - 6.86 kcal/mol and - 5.39 kcal/mol for hAChE receptor. Derivatives indicated estimated free binding energies in the range between - 6.42 kcal/mol and - 7.96 kcal/mol for hBuChE. Besides reactivity descriptors and drug-likeness characters of compounds were analyzed. All derivatives were predicted to have no violation of Lipinski's rule of five.

Journal

CHEMICAL PAPERS

Year

2026

Volume

80

Issue

1

Pages

633-644

ISSN

0366-6352

eISSN

2585-7290

DOI

10.1007/s11696-025-04417-6

WoS UID

WOS:001594899400001