Synthesis of 4,5-disubstituted-2-thioxo-1,2,3,4-tetrahydropyrimidines and investigation of their acetylcholinesterase, butyrylcholinesterase, carbonic anhydrase I/II inhibitory and antioxidant activities

Abstract

A series of tetrahydropyrimidinethiones were synthesized from thiourea, β-diketones and aromatic aldehydes, such as p-tolualdehyde, p-anisaldehyde, o-tolualdehyde, salicylaldehyde and benzaldehyde. These cyclic thioureas showed good inhibitory action against acetylcholine esterase (AChE), butyrylcholine esterase (BChE), and human (h) carbonic anhydrase (CA) isoforms I and II. AChE and BChE inhibitions were in the range of 6.11–16.13 and 6.76–15.68 nM, respectively. hCA I and II were effectively inhibited by these compounds, with K_i values in the range of 47.40–76.06 nM for hCA I, and of 30.63–76.06 nM for hCA II, respectively. The antioxidant activity of the cyclic thioureas was investigated by using different in vitro antioxidant assays, including 1,1-diphenyl-2-picrylhydrazyl (DPPH·) radical scavenging, Cu²⁺and Fe³⁺reducing, and Fe²⁺chelating activities.

Keywords:

• Acetylcholinesterase
• antioxidant activity
• butyrylcholinesterase
• carbonic anhydrase
• enzyme inhibition

Declaration of interest

The authors have declared no conflict of interest.

IG and SA would like to extend his sincere appreciation to the Research Chairs Program at King Saud University for funding this research.