Scrutiny of Novel Tosylacrylimidamide as Non‐Classical Bioisosteres of Sulfonylurea in Type II Diabetes Mellitus through Synthesis, In Vitro and Docking Studies

Abstract

Sulfonylureas is being used throughout the world for the treatment of diabetes mellitus. The aim of the present study was to investigate mode of action of tosylacrylimidamide. Tosylacrylimidamide a non-classical bioisosteres of sulfonyl urea, bioisosteres refer to structurally distinct molecules eliciting a similar biological effect. In the present study we have determined the ability of tosylacrylimidamide to stimulate insulin secretion from MIN-6 cells. The compounds were tested in the presence of 5 mM glucose concentration, our results indicates that compound 4 e, 4 f, 4 g were the most effective insulin secretagogue's amongst reported, then 4 e, 4 f, 4 g were further evaluated at various concentration of compound keeping glucose concentration constant (5 mM), resulting 4 e showed 4.34 fold increase in insulin secretion at 1 mg/ml of compound, 4 f showed 7.4 fold increase in insulin secretion at 5 mg/ml of compound and 4 g has shown 7.6 fold increase in insulin secretion at 5 mg/ml of compound. The rest of the tosylacrylimidamide in our assay had only marginal effects on insulin secretion[a] S.

Synthesis of Novel Methylsulfonylacrylimidamide via Click Chemistry approach, Computational analysis and α- glucosidase inhibition activity

“…Acrylamidine is an important synthetic precursor of amidine, which is present in various bioactive compounds such as selective muscarinic agonists and NR2B subtype-selective antagonists, among others [11]. Acrylamidine displays a wide spectrum of pharmacological activities such as anticancer and insulin-releasing properties [12].…”

Synthesis of Novel Methylsulfonylacrylimidamide via Click Chemistry Approach, Computational Analysis and α‐ Glucosidase Inhibition Activity

“…Acrylamidine is an important synthetic precursor of amidine, which is present in various bioactive compounds such as selective muscarinic agonists and NR2B subtype‐selective antagonists, among others [11] . Acrylamidine displays a wide spectrum of pharmacological activities such as anticancer and in our previous study we have reported insulin‐releasing properties [12] . Based on the multiple pharmacological activities of acrylamidines as biologically active molecules, this study aimed to design and synthesize new methylsulfonylacrylimidamide derivatives and evaluate their α ‐glucosidase inhibitory activity.…”

“…[11] Acrylamidine displays a wide spectrum of pharmacological activities such as anticancer and in our previous study we have reported insulin-releasing properties. [12] Based on the multiple pharmacological activities of acrylamidines as biologically active molecules, this study aimed to design and synthesize new methylsulfonylacrylimidamide derivatives and evaluate their α-glucosidase inhibitory activity. In the present study, we report the design, synthesis, and αglucosidase inhibitory activity studies of novel methylsulfonylacrylimidamide derivatives.…”