RESUMO
In this study, compounds with 4-hydroxybutyl, 4-phenyl, 5-carboxylate, and pyrimidine moieties were determined as α-glycosidase inhibitors. N-Substituted pyrimidinethione and acetophenone derivatives (A1-A5, B1-B11, and C1-C11) were good inhibitors of the α-glycosidase enzyme, with Ki values in the range of 104.27 ± 15.75 to 1,004.25 ± 100.43 nM. Among them, compound B7 was recorded as the best inhibitor, with a Ki of 104.27 ± 15.75 nM against α-glycosidase. In silico studies were carried out to clarify the binding affinity and interaction mode of the compounds with the best inhibition score against α-glycosidase from Saccharomyces cerevisiae. Compounds B7 (S) and B11 (R) exhibited a good binding affinity with docking scores of -8.608 and 8.582 kcal/mol, respectively. The docking results also showed that the 4-hydroxybutyl and pyrimidinethione moieties play a key role in S. cerevisiae and human α-glycosidase inhibition.
Assuntos
Acetofenonas/farmacologia , Hipoglicemiantes/farmacologia , Pirimidinas/farmacologia , Acetofenonas/síntese química , Acetofenonas/química , Diabetes Mellitus/tratamento farmacológico , Inibidores de Glicosídeo Hidrolases/síntese química , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Humanos , Hipoglicemiantes/síntese química , Hipoglicemiantes/química , Simulação de Acoplamento Molecular , Pirimidinas/síntese química , Pirimidinas/química , Saccharomyces cerevisiae/enzimologia , Relação Estrutura-Atividade , Tionas/síntese química , Tionas/química , Tionas/farmacologiaRESUMO
In the presence of trifluoroacetic acid, on the basis of three-component condensation of phenylthiourea with its salicylaldehyde and methyl-3-oxobutanoate, an efficient method for the synthesis of 1-(4-(2-hydroxyphenyl)-6-methyl-1-phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidin-5-yl)ethanone (I) has been worked out. These novel N-substituted tetrahydropyrimidines based on phenylthiourea showed good inhibitory action against acetylcholinesterase (AChE), α-glycosidase, and human carbonic anhydrase (hCA) isoforms I and II. K i values of AChE enzyme were in the range of 0.48 to 7.46 nM. The hCA I and II were effectively inhibited by the compounds, with K i values in the range of 502.44 to 923.11 nM for hCA I and 400.32 to 801.57 nM for hCA II, respectively. The antioxidant activity of the novel N-substituted tetrahydropyrimidines based on phenylthiourea was investigated by using different in vitro antioxidant assays; including 1,1-diphenyl-2-picrylhydrazyl (DPPH·) radical scavenging, Cu 2+ and Fe 3+ reducing activities.