Glutathione Peroxidase-like Antioxidant Activity of 1,3-Benzoselenazoles: Synthesis and In Silico Molecular Docking Studies as Pancreatic Lipase Inhibitors.

Abstract

The synthesis of 1,3-benzoselenazoles was achieved by the reaction of corresponding bis[3-amino-N-(p-tolyl)benzamide-2-yl] diselenide, bis[3-amino-N-(4-methoxyphenyl)benzamide-2-yl] diselenide, and bis[3-amino-N-(4-(dimethylamino)phenyl) benzamide-2-yl] diselenide with aryl aldehydes. The 1,3-benzoselenazoles continued to exist as planar molecules due to the presence of secondary Se···O interactions as revealed by the single-crystal X-ray analysis. The presence of secondary Se···O interactions in 1,3-benzoselenazoles was confirmed using natural bond orbital (NBO) and atoms in molecules (AIM) calculations. Nucleus-independent chemical shift (NICS) values suggested the presence of aromatic character in a five-membered benzoselenazole heterocyclic ring. The glutathione peroxidase (GPx)-like antioxidant activity of all 1,3-benzoselenazoles was assessed using a thiophenol assay, exhibiting greater antioxidant activity than Ph2Se2 used as a reference. The most active catalyst carrying a strong electron-donating group (-NMe2) at the ortho-position to the benzoselenazole ring was further investigated at different concentrations of thiophenol, H2O2, and 1,3-benzoselenazoles as catalyst for determining their catalytic parameters. Moreover, the potential applications of all 1,3-benzoselenazoles against pancreatic lipase (PL) have been identified using in silico interactions between the active sites of the 1LPB protein as evaluated using a molecular docking study.