Selenourea and thiourea derivatives of chiral and achiral enetetramines: Synthesis, characterization and enzyme inhibitory properties

Abstract

A series of chiral and achiral cyclic seleno- and thiourea compounds bearing benzyl groups on N-atoms were prepared from enetetramines and appropriate Group VI elements in good yields. All the synthesized compounds were characterized by elemental analysis, FT-IR, ¹H NMR and ¹³C NMR spectroscopy, and the molecular and crystal structures of (R,R)-4b and (R,R)-5b were confirmed by the single-crystal X-ray diffraction method. These assayed for their activities against metabolic enzymes acetylcholinesterase, butyrylcholinesterase, and α-glycosidase. These selenourea and thiourea derivatives of chiral and achiral enetetramines effectively inhibit AChE and BChE with IC₅₀ values in the range of 3.32-11.36 and 1.47-9.73 µM, respectively. Also, these compounds inhibited α-glycosidase enzyme with IC₅₀ values varying between 1.37 and 8.53 µM. The results indicated that all the synthesized compounds exhibited excellent inhibitory activities against mentioned enzymes as compared with standard inhibitors. Representatively, the most potent compound against α-glycosidase enzyme, (S,S)-5b, was 12-times more potent than standard inhibitor acarbose; 7b and 8a as most potent compounds against cholinesterase enzymes, were around 5 and 13-times more potent than standard inhibitor tacrine against achethylcholinesterase (AChE) and butyrylcholinesterase (BChE), respectively.

Keywords: Achethylcholinesterase; Butyrylcholinesterase; Chiral selenourea; Crystal structure; Enetetramine; Enzyme inhibition; Thiourea.