Synthesis, characterization, DFT studies and molecular docking investigation of 2-oxo-ethyl piperidine pentanamide-derived sulfonamides as anti-diabetic agents

Abstract

The present study is focused on the synthesis, characterization, DFT Studies, and in silico biological evaluation of novel benzenesulfonamides as antidiabetic agents. The compounds were synthesized and characterized experimentally using the NMR, FT-IR and HRMS while the molecular electronic structure properties were investigated using DFT-based theoretical methods at the M06-2X/6–311++G (d, p) level of theory. The results of the calculated vibrational energies were in perfect agreement with those of the experimental frequencies for different functional groups. The natural bond orbital (NBO) analysis was also carried out to study the intramolecular charge transfer interactions and energies of stabilization. Molecular docking simulation showed that the compounds; 3-Methyl-2-(4-methylphenylsulfonamido)-N-(2-oxo-2(piperidin-1-yl) ethyl) pentanamide (MMOPEP), 3-Methyl-N-(2-oxo-2-(piperidin-1-yl)ethyl))-2-(phenylsulfonamido)pentanamide (MOPEPP) and, 3-Methyl-2-(4-nitrophenylsulfonamido)-N-(2-oxo-2-(piperidin-1-yl)ethyl)pentanamide (MNOPEP) fitted tightly to the amino acid residues binding sites of insulin inhibiting protein receptors (7m17) with an average binding affinity of −6.9 kcal/mol, −6.6 kcal/mol, −6.7 kcal/mol respectively, thereby stimulating the release of insulin from functioning pancreatic beta cells which will in turn, lower blood glucose. This study provides a platform for scrutiny and clinical trials of benzenesulfonamide-based drugs as antidiabetic agents.

Keywords

• Anti-diabetic
• Synthesis
• Sulfonamides
• Piperidine
• DFT
• Molecular docking