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 1H NMR, 13C NMR, and HRMS 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 5b (23.89 µM), 5i (28.87 µM), and 5f (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 5b (‐8.7 kcal/mol), 5i (‐8.6 kcal/mol), and 5f (‐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 5a, 5b, 5c, and 5d. 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 5f was observed to be the best inhibitor for pancreatic lipase according to in vitro and in silico studies.

Biaryl carboxamide‐based peptidomimetics analogs as potential pancreatic lipase inhibitors for treating obesity

“…Recently, it has been reported that novel synthetic tyrosinase inhibitors, such as aryl sulfonate-naphthalene hybrid, benzothiazole sulfonate compounds bearing azomethine and bis (sulfonate) derivatives, have displayed potent inhibitory activity against PL through in vitro PL assay. [31,32] In contrast, ethanolic extract of the natural product Spartina anglica, which exhibits tyrosinase inhibition activity, has demonstrated significant in vitro PL inhibitory activity. [33] Interestingly, in silico studies revealed that carboxamide analogs bind to the active site of the PL and inhibit it.…”