In Silico and in Vitro Biological Evaluation of Novel Serial Sulfonate Derivatives on Pancreatic Lipase Activity.

Abstract

The novel benzothiazole sulfonate hybrid derivatives containing azomethine group were synthesized and characterized using 1 H-NMR, 13 C-NMR, and HR-MS analysis. The potential enzyme inhibition activities against pancreatic lipase of the novel benzothiazole sulfonate hybrid derivatives containing azomethine group were screened with in vitro and in silico methods. IC50 values of compounds 5 b (23.89 μM), 5 i (28.87 μM), and 5 f (30.13±4.32) were found to be more effective pancreatic lipase inhibitors than orlistat (57.75 μM) in vitro studies. Also, the binding affinities of compounds 5 b (-8.7 kcal/mol), 5 i (-8.6 kcal/mol), and 5 f (-8.9 kcal/mol) were found potential inhibitors for pancreatic lipase in silico studies. In addition, the absorption distribution, metabolism, and excretion properties (ADME), molecular properties, toxicity estimation, and bioactivity scores of the synthesized compounds were scanned. It was found to have the ability to cross the brain-blood barrier for compounds 5 a, 5 b, 5 c, and 5 d. All compounds were calculated to be taken orally as drugs, suitable for absorption in the intestinal tract and not carcinogenic, as well as very strongly bound to plasma proteins. Finally, compound 5 f was observed to be the best inhibitor for pancreatic lipase according to in vitro and in silico studies.