An in vitro and in silico study on the synthesis and characterization of novel bis(sulfonate) derivatives as tyrosinase and pancreatic lipase inhibitors

Herein, we present a straightforward synthetic strategy mediated by triethylamine to prepare the target salicylaldehyde functional group's bearing bis(sulfonate) derivatives. The novel bis(sulfonate) derivatives (compounds 2a-i) were designed, synthesized, and characterized for the first time. The structures of compounds were determined by H-1 NMR, C-13 NMR, and HRMS techniques. Enzyme inhibition effects and enzyme interactions of compounds were evaluated on tyrosinase and pancreatic lipase enzymes by using in silico and in vitro methods. According to the enzyme assays, compound 2h had more effective inhibition against the pancreatic lipase enzyme with a lower IC50 value (53.3 +/- 2.7 mu M) than the other compounds. On the other hand, two of the newly synthesized compounds ( 2f and 2h) had effective inhibitions against the tyrosinase enzyme with having (49.5 +/- 2.5 mu M) IC50 values. In addition, molecular docking studies were performed to determine the interactions and binding energy levels of the bis(sulfonate) derivatives with tyrosinase and pancreatic lipase. Also, additional ADME studies of the bis(sulfonate) compounds were evaluated. (c) 2022 Elsevier B.V. All rights reserved.

Automated summary

A straightforward synthetic strategy mediated by triethylamine was used to prepare bis(sulfonate) derivatives bearing the target salicylaldehyde functional group. The novel compounds (2a-i) were designed, synthesized, and characterized. Enzyme inhibition effects and interactions with tyrosinase and pancreatic lipase were evaluated using computational and experimental methods. Compound 2h showed the most effective inhibition against pancreatic lipase, while compounds 2f and 2h exhibited significant inhibitions against tyrosinase. Molecular docking studies and ADME evaluations were conducted to investigate the interactions and pharmacokinetic properties of the bis(sulfonate) derivatives.