Design and Synthesis of Alpha Glycosidase Inhibitors for 1-Benzyl-4-oxa-1,9-diazaspiro[5.5]undecan-2-one as an Antidiabetic Agent

Abstract

A series of (4-(trifluoromethyl)benzyl)-linked 1,9-diazaspiro[5.5]undecane derivatives were designed as α-glucosidase inhibitors. We have synthesized new (4-(trifluoromethyl)benzyl)-linked 1,9-diazaspiro derivatives for their antidiabetes properties. The newly synthesized compounds were examined for their inhibition activity against α-glucosidase. The findings demonstrated that the novel synthesized compounds inhibited significantly against α-glucosidase. Among them, SPO-7 and SPO-9 demonstrated the most potent inhibition, with IC₅₀ values of 49.96 and 63.15 nmol, respectively. Docking studies examined the orientation, interaction, and verification of the intent compounds on the active site of α-glucosidase. The compounds SPO-7 and SPO-9 exhibit the highest docking energies, with values of −10.7 and −10.6 kcal/mol, respectively. In addition, the compound SPO-7 exhibited substantial inhibition effects at all tested concentrations and their capacity to inhibit the bacterial activity against Escherichia coli and Bacillus cereus. The minimum inhibitory concentration (MIC) values for SPO-7 and SPO-11 were determined to be 0.156 mg/mL. Furthermore, computational drug-likeness/ADME/toxicity tests were conducted on the compounds, which indicated that this compound exhibits drug-like properties and possesses favorable ADME and toxicity profiles.