Benzofuran-selenadiazole hybrids as novel α-glucosidase and cyclooxygenase-2 inhibitors with antioxidant and cytotoxic properties

• Published in: Bioorganic chemistry 2020-07, Vol.100, p.103945, Article 103945
• Main Authors: Olomola, Temitope O., Mphahlele, Malose J., Gildenhuys, Samantha
• Format: Article
• Language: English
• Subjects: alpha-Glucosidases - chemistry; alpha-Glucosidases - metabolism; Antioxidants - chemistry; Azoles - chemistry; Benzofurans - chemistry; Binding Sites; Catalytic Domain; Cell Line; Cell Survival - drug effects; Cyclooxygenase 2 - chemistry; Cyclooxygenase 2 - metabolism; Cyclooxygenase 2 Inhibitors - chemistry; Cyclooxygenase 2 Inhibitors - metabolism; Cyclooxygenase 2 Inhibitors - pharmacology; Cyclooxygenase-2, antioxidant activity; Cytotoxicity; Glycoside Hydrolase Inhibitors - chemistry; Glycoside Hydrolase Inhibitors - metabolism; Glycoside Hydrolase Inhibitors - pharmacology; Humans; Kinetics; Lipopolysaccharides - pharmacology; MCF-7 Cells; Molecular Conformation; Molecular docking; Molecular Docking Simulation; Reactive Oxygen Species - metabolism; Selenadiazol-4-yl-benzofurans; Structure-Activity Relationship; α-glucosidase
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2020.103945

[Display omitted] •Novel benzofuran-appended 1,2,3-selenadiazoles have been evaluated against several targets linked to type 2 diabetes.•The molecular hybrids exhibit increased activity against α-glucosidase and cyclooxygenase-2.•These multifunctional ligands exhibit free radical scavenging properties.•Kinetic and molecular docking studies were also undertaken. Series of 2-arylbenzofuran–1,2,3-selenodiazole hybrids were prepared via multiple reactions and then evaluated in vitro through enzymatic assay for inhibitory effect against α-glucosidase and cyclooxygenase-2 (COX-2) activities including antioxidant activity. The presence of 1,2,3-selenodiazole moiety resulted in increased inhibitory effect for compounds 4a–f against α-glucosidase and COX-2 activities, and increased free radical scavenging activity. 6-Acetoxy-2-phenyl-5-(1,2,3-selenadiazol-4-yl)benzofuran (4a) and its 2-(4-methoxyphenyl) substituted derivative (4f) were, in turn, screened for antiproliferation against the breast MCF-7 cancer cell line and for cytotoxicity on the human embryonic kidney derived Hek293-T cells. A cell-based antioxidant activity assay involving lipopolysaccharide induced reactive oxygen species production in these cells was performed. Molecular docking has also been performed on these two compounds to predict protein–ligand interactions against α-glucosidase and COX-2.