Design and synthesis of thiophenone and furanthione butenolide bioisosteres with inhibitory activity towards acetylcholinesterase

•A library of butenolide bioisosteres was synthetized.•Synthetic strategies were based on bioisosteric exchange of oxygen for Sulfur.•Nucleophilic alkylation resulted in differential binding with acetylcholinesterase.•A new C5 disubstituted furan-2(5H)-thione was identified as a promising inhibitor.•Toxicity, dynamics and quantum states were determined.