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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2021-12-01
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| 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. |
| format | Article |
| id | doaj-art-b806ce13cfaf40eaa0d7136e89ddc05c |
| institution | Kabale University |
| issn | 1846-9558 |
| language | English |
| publishDate | 2021-12-01 |
| publisher | Sciendo |
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| series | Acta Pharmaceutica |
| 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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