Novel cyclic thiourea derivatives of aminoalcohols at the presence of AlCl3 catalyst as potent alpha-glycosidase and alpha-amylase inhibitors: Synthesis, characterization, bioactivity investigation and molecular docking studies

The article is devoted to the targeted synthesis and study of cyclic thiourea and their various new derivatives as new organic compounds containing polyfunctional group in the molecule. First time the reaction of the corresponding synthesized pyrimidinethione with 1,2-epoxy-3-chlorpropane at the presence of AlCl3 catalyst in 75-80 yield alkyl-1-(3-chloro-2-hydroxypropyl)-4-alkyl-6-phenyl-2-thioxo-1,2,5,6- tetrahydropyrimidine-5-carboxylates. In the next stage, new cyclic thiourea derivatives of aminoalcohols were synthesised from the reaction of chlorinated derivatives of pyrimidinethiones with single amines and their structures were investigated by spectroscopic methods. In this study, a series of novel compounds were tested towards some metabolic enzymes including alpha-glycosidase (alpha-Gly) and alpha-amylase (alpha-Amy) enzymes. Novel compounds showed Kis in ranging of 10.43 +/- 0.94-111.37 +/- 13.25 microM on alpha-glycosidase and IC50 values in ranging of 14.38-106.51 microM on alpha-amylase. The novel cyclic thiourea derivatives of aminoalcohols had effective inhibition profiles against all tested metabolic enzymes. Binding affinity and inhibition mechanism of the most active compounds were detected with in silico studies and have shown that 2-Hydroxypropyl and butan-1-aminium moieties play a key role for inhibition of the enzymes

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

A series of tetrahydropyrimidinethiones were synthesized from thiourea, -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 6.76-15.68nM, respectively. hCA I and II were effectively inhibited by these compounds, with K-i values in the range of 47.40-76.06nM for hCA I, and of 30.63-76.06nM 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, Cu(2+)and Fe(3+)reducing, and Fe(2+)chelating activities