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

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)...

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Main Authors: Khalaf Reema Abu, Alwarafi Ebtisam, Sabbah Dima
Format: Article
Language:English
Published: Sciendo 2021-12-01
Series:Acta Pharmaceutica
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Online Access:https://doi.org/10.2478/acph-2021-0034
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author Khalaf Reema Abu
Alwarafi Ebtisam
Sabbah Dima
author_facet Khalaf Reema Abu
Alwarafi Ebtisam
Sabbah Dima
author_sort Khalaf Reema Abu
collection DOAJ
description 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.
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spelling doaj-art-b806ce13cfaf40eaa0d7136e89ddc05c2025-02-02T22:59:43ZengSciendoActa Pharmaceutica1846-95582021-12-0171463164310.2478/acph-2021-0034Piperazine sulfonamides as DPP-IV inhibitors: Synthesis, induced-fit docking and in vitro biological evaluationKhalaf Reema Abu0Alwarafi Ebtisam1Sabbah Dima2Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman, JordanDepartment of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman, JordanDepartment of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman, JordanDiabetes 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.https://doi.org/10.2478/acph-2021-0034piperazine sulfonamidedipeptidyl peptidase-iv inhibitordiabetes mellitusinduced-fit docking
spellingShingle Khalaf Reema Abu
Alwarafi Ebtisam
Sabbah Dima
Piperazine sulfonamides as DPP-IV inhibitors: Synthesis, induced-fit docking and in vitro biological evaluation
Acta Pharmaceutica
piperazine sulfonamide
dipeptidyl peptidase-iv inhibitor
diabetes mellitus
induced-fit docking
title Piperazine sulfonamides as DPP-IV inhibitors: Synthesis, induced-fit docking and in vitro biological evaluation
title_full Piperazine sulfonamides as DPP-IV inhibitors: Synthesis, induced-fit docking and in vitro biological evaluation
title_fullStr Piperazine sulfonamides as DPP-IV inhibitors: Synthesis, induced-fit docking and in vitro biological evaluation
title_full_unstemmed Piperazine sulfonamides as DPP-IV inhibitors: Synthesis, induced-fit docking and in vitro biological evaluation
title_short Piperazine sulfonamides as DPP-IV inhibitors: Synthesis, induced-fit docking and in vitro biological evaluation
title_sort piperazine sulfonamides as dpp iv inhibitors synthesis induced fit docking and in vitro biological evaluation
topic piperazine sulfonamide
dipeptidyl peptidase-iv inhibitor
diabetes mellitus
induced-fit docking
url https://doi.org/10.2478/acph-2021-0034
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