Design, Synthesis, Characterization and Biological Activities of Novel S‐(Acyloxy)butyl‐N,N‐Diethyldithiocarbamate Compounds

Abstract

In this study, S‐(Acyloxy)butyl‐N,N‐Diethyldithiocarbamate compounds (P1‐P7) were synthesized by s‐alkylation of N,N‐diethyldithiocarbamate sodium trihydrate with 4‐chlorobutylcarboxylates. P1–P7 were characterized by full infrared, NMR spectroscopy and elemental analyses. Additionally, the impacts of these compounds were investigated on some metabolic enzymes and then compared to the reference compounds. It was observed that the DEDTCA esters generally had lower IC50 and Ki values. Among them, P4 and P6 molecules had lower IC50 with 112.47 and 111.55 μM; and Ki values: 105.53±7.17 and 102.06±5.08 μM against AChE, respectively. Furthermore, molecular docking simulations approved the binding interaction patterns and structural orientations of N,N‐diethyldithiocarbamic acid derivatives within the binding sites of AChE, BChE and α‐glucosidase. Taken together, the compound P6 performs strong distant bond interactions against tacrine for AChE and BChE enzymes within the scope of in silico study. The compound P4, on the other hand, exhibits good interactions with the target by making hydrophobic, pi‐sulfur and pi‐sigma bonds as well as hydrogen bonds compared to acarbose as standard compound against α‐glucosidase. These can be further analyzed as potent candidate compounds in biological studies of the respective enzymes.