<abstract xmlns="http://www.w3.org/1999/xhtml">Diabetes mellitus is a chronic illness that needs persistent medical attention and continuous patient self-management to avoid acute complications. Dipeptidyl peptidase-IV (DPP-IV) inhibitors minimize glucagon and blood glucose levels by increasing the incretin levels, glucagon-like peptide (GLP-1) and glucose-dependent insulinotropic poly-peptide (GIP), leading to insulin secretion from pancreatic beta cells. In the present study, nine 1,4-bis(phenylsulfonyl) piperazine derivatives <bold>1a</bold>-<bold>i</bold> were synthesized and identified using 1H NMR, 13C NMR, MS and IR spectroscopies. These compounds were tested <italic>in vitro</italic> and showed inhibitory activity ranging from 11.2 to 22.6 % at 100 µmol L–1 concentration. Piperazine sulfonamide derivatives were found to be promising DPP-IV inhibitors, where the presence of electron-withdrawing groups such as Cl (<bold>1a</bold>-<bold>c</bold>) improved the activity of the compounds more than electron-donating groups such as CH3 (<bold>1d</bold>-<bold>f</bold>) at the same position. Additionally, <italic>meta</italic>-substitution is disfavored (<bold>1b</bold>, <bold>1e</bold>, <bold>1g</bold>). Induced-fit docking studies suggested that the targeted compounds <bold>1a</bold>-<bold>i</bold> occupy the binding domain of DPP-IV and form H-bonding with the backbones of R125, E205, E206, F357, K554, W629, Y631, Y662 and R669.</abstract>

Diabetes mellitus is a chronic illness that needs persistent medical attention and continuous patient self-management to avoid acute complications. Dipeptidyl peptidase-IV (DPP-IV) inhibitors minimize glucagon and blood glucose levels by increasing the incretin levels, glucagon-like peptide (GLP-1) and glucose-dependent insulinotropic poly-peptide (GIP), leading to insulin secretion from pancreatic beta cells. In the present study, nine 1,4-bis(phenylsulfonyl) piperazine derivatives 1a-i were synthesized and identified using 1H NMR, 13C NMR, MS and IR spectroscopies. These compounds were tested in vitro and showed inhibitory activity ranging from 11.2 to 22.6 % at 100 µmol L–1 concentration. Piperazine sulfonamide derivatives were found to be promising DPP-IV inhibitors, where the presence of electron-withdrawing groups such as Cl (1a-c) improved the activity of the compounds more than electron-donating groups such as CH3 (1d-f) at the same position. Additionally, meta-substitution is disfavored (1b, 1e, 1g). Induced-fit docking studies suggested that the targeted compounds 1a-i occupy the binding domain of DPP-IV and form H-bonding with the backbones of R125, E205, E206, F357, K554, W629, Y631, Y662 and R669.

Piperazine sulfonamides as DPP-IV inhibitors: Synthesis, induced-fit docking and <italic>in vitro</italic> biological evaluation

Department of Pharmacy, Faculty of Pharmacy

Acta Pharmaceutica

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Piperazine sulfonamides as DPP-IV inhibitors: Synthesis, induced-fit docking and  biological evaluation

Diabetes mellitus is a chronic illness that needs persistent medical attention and continuous patient self-management to avoid acute complications. Dipeptidyl...

Piperazine sulfonamides as DPP-IV inhibitors: Synthesis, induced-fit docking and in vitro biological evaluation

Publicado en línea: 03 abr 2021

Páginas: 631 - 643

Aceptado: 20 oct 2020

DOI: https://doi.org/10.2478/acph-2021-0034

Palabras clave
piperazine sulfonamide, dipeptidyl peptidase-IV inhibitor, diabetes mellitus, induced-fit docking

© 2021 Reema Abu Khalaf et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Piperazine sulfonamides as DPP-IV inhibitors: Synthesis, induced-fit docking and in vitro biological evaluation

Publicado en línea: 03 abr 2021

Páginas: 631 - 643

Aceptado: 20 oct 2020

DOI: https://doi.org/10.2478/acph-2021-0034

Palabras clavepiperazine sulfonamide, dipeptidyl peptidase-IV inhibitor, diabetes mellitus, induced-fit docking

© 2021 Reema Abu Khalaf et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Palabras clave
piperazine sulfonamide, dipeptidyl peptidase-IV inhibitor, diabetes mellitus, induced-fit docking