Work

Design, synthesis, and docking analysis of benzene sulfonamide-[1,4]benzoxazepine hybrids as acetylcholinesterase and butyrylcholinesterase inhibitors

Year: 2026

Type: article

Abstract: = 4.18 ± 0.56 µM; SI = 14.94). Molecular docking studies revealed plausible binding modes of the active compounds within the AChE and BChE active sites, involving π-π stacking, hydrogen bonding, and hydrophobic interactions. The SAR analysis indicated that the effects of nitro and halogen substituents were scaffold- and position-dependent, with selected nitro-substituted derivatives showing enhanced cholinesterase inhibition, whereas brominated analogs exhibited a pronounced preference toward BChE. Integration of the biological and computational data identified compounds 9a, 9b, 9d, 12b, 12j, and 12j as promising candidates for further investigation. Among these, 12j represents the potency lead for BChE inhibition, whereas 9d provides the most pronounced BChE selectivity. ADMET predictions further suggested more favorable physicochemical and pharmacokinetic profiles for selected benzoxazepine-based derivatives, although potential toxicity liabilities were predicted for 12j. Overall, these findings support the [1,4]benzoxazepine-sulfonamide scaffold as a promising starting point for developing BChE-preferring cholinesterase inhibitors.

Source: RSC Advances

DOI: 10.1039/d6ra08312a

Authors: Almeqdad Y. Habashneh, Muhammad Ashram, Wafa Hourani, Mahmoud A. Al-Sha'er, Murad A. AlDamen

Institutions: University of Jordan, Mutah University, Philadelphia University, Zarqa University

Language: English

Topic: Cholinesterase and Neurodegenerative Diseases

Subfield: Pharmacology (medical)

Field: Medicine

Domain: Health Sciences

Open Access status: gold

Estimated APC paid: $1,042

Funders: University of Jordan, Zarqa University