Synthesis, molecular docking, and anti-inflammatory evaluation of novel 4-(benzo[d][1,3]dioxol-5-yloxy)-N,N-2-yn-1-amine derivatives as potent cysteinyl leukotriene receptor (CysLT2) antagonists
Cysteinyl leukotrienes (CysLTs), derived from arachidonic acid, play a crucial role in regulating inflammation. We synthesized a novel series of CysLT2 antagonists containing the benzo[d][1,3]dioxole moiety using a synthetic strategy based on the Mannich reaction, resulting in the formation of 4-(be...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Pensoft Publishers
2025-02-01
|
| Series: | Pharmacia |
| Online Access: | https://pharmacia.pensoft.net/article/143171/download/pdf/ |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850184021137424384 |
|---|---|
| author | Areej M. Jaber Mohammed M. Al-Mahadeen Belal O. Al-Najjar Raed A. Al-Qawasmeh |
| author_facet | Areej M. Jaber Mohammed M. Al-Mahadeen Belal O. Al-Najjar Raed A. Al-Qawasmeh |
| author_sort | Areej M. Jaber |
| collection | DOAJ |
| description | Cysteinyl leukotrienes (CysLTs), derived from arachidonic acid, play a crucial role in regulating inflammation. We synthesized a novel series of CysLT2 antagonists containing the benzo[d][1,3]dioxole moiety using a synthetic strategy based on the Mannich reaction, resulting in the formation of 4-(benzo[d][1,3]dioxol-5-yloxy)-N,N-2-yn-1-amine. The structures of the synthesized compounds were characterized through NMR and HRMS analyses, and a plausible reaction mechanism was proposed. The inhibitory activities of all new compounds against CysLT2 were evaluated in vitro. Among them, compounds 4d and 4g exhibited the most potent inhibitory effects, with IC50 values of 18.7 μM and 15.5 μM, respectively. These findings were further supported by molecular docking studies, which highlighted the binding interactions of these compounds within the kinase’s active site. Graphical abstract: |
| format | Article |
| id | doaj-art-f17a835b1bfc4375be1bd523314d0607 |
| institution | OA Journals |
| issn | 2603-557X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Pensoft Publishers |
| record_format | Article |
| series | Pharmacia |
| spelling | doaj-art-f17a835b1bfc4375be1bd523314d06072025-08-20T02:17:09ZengPensoft PublishersPharmacia2603-557X2025-02-017211110.3897/pharmacia.72.e143171143171Synthesis, molecular docking, and anti-inflammatory evaluation of novel 4-(benzo[d][1,3]dioxol-5-yloxy)-N,N-2-yn-1-amine derivatives as potent cysteinyl leukotriene receptor (CysLT2) antagonistsAreej M. Jaber0Mohammed M. Al-Mahadeen1Belal O. Al-Najjar2Raed A. Al-Qawasmeh3Al-Ahliyya Amman UniversityThe University of JordanAl-Ahliyya Amman UniversityUniversity of SharjahCysteinyl leukotrienes (CysLTs), derived from arachidonic acid, play a crucial role in regulating inflammation. We synthesized a novel series of CysLT2 antagonists containing the benzo[d][1,3]dioxole moiety using a synthetic strategy based on the Mannich reaction, resulting in the formation of 4-(benzo[d][1,3]dioxol-5-yloxy)-N,N-2-yn-1-amine. The structures of the synthesized compounds were characterized through NMR and HRMS analyses, and a plausible reaction mechanism was proposed. The inhibitory activities of all new compounds against CysLT2 were evaluated in vitro. Among them, compounds 4d and 4g exhibited the most potent inhibitory effects, with IC50 values of 18.7 μM and 15.5 μM, respectively. These findings were further supported by molecular docking studies, which highlighted the binding interactions of these compounds within the kinase’s active site. Graphical abstract:https://pharmacia.pensoft.net/article/143171/download/pdf/ |
| spellingShingle | Areej M. Jaber Mohammed M. Al-Mahadeen Belal O. Al-Najjar Raed A. Al-Qawasmeh Synthesis, molecular docking, and anti-inflammatory evaluation of novel 4-(benzo[d][1,3]dioxol-5-yloxy)-N,N-2-yn-1-amine derivatives as potent cysteinyl leukotriene receptor (CysLT2) antagonists Pharmacia |
| title | Synthesis, molecular docking, and anti-inflammatory evaluation of novel 4-(benzo[d][1,3]dioxol-5-yloxy)-N,N-2-yn-1-amine derivatives as potent cysteinyl leukotriene receptor (CysLT2) antagonists |
| title_full | Synthesis, molecular docking, and anti-inflammatory evaluation of novel 4-(benzo[d][1,3]dioxol-5-yloxy)-N,N-2-yn-1-amine derivatives as potent cysteinyl leukotriene receptor (CysLT2) antagonists |
| title_fullStr | Synthesis, molecular docking, and anti-inflammatory evaluation of novel 4-(benzo[d][1,3]dioxol-5-yloxy)-N,N-2-yn-1-amine derivatives as potent cysteinyl leukotriene receptor (CysLT2) antagonists |
| title_full_unstemmed | Synthesis, molecular docking, and anti-inflammatory evaluation of novel 4-(benzo[d][1,3]dioxol-5-yloxy)-N,N-2-yn-1-amine derivatives as potent cysteinyl leukotriene receptor (CysLT2) antagonists |
| title_short | Synthesis, molecular docking, and anti-inflammatory evaluation of novel 4-(benzo[d][1,3]dioxol-5-yloxy)-N,N-2-yn-1-amine derivatives as potent cysteinyl leukotriene receptor (CysLT2) antagonists |
| title_sort | synthesis molecular docking and anti inflammatory evaluation of novel 4 benzo d 1 3 dioxol 5 yloxy n n 2 yn 1 amine derivatives as potent cysteinyl leukotriene receptor cyslt2 antagonists |
| url | https://pharmacia.pensoft.net/article/143171/download/pdf/ |
| work_keys_str_mv | AT areejmjaber synthesismoleculardockingandantiinflammatoryevaluationofnovel4benzod13dioxol5yloxynn2yn1aminederivativesaspotentcysteinylleukotrienereceptorcyslt2antagonists AT mohammedmalmahadeen synthesismoleculardockingandantiinflammatoryevaluationofnovel4benzod13dioxol5yloxynn2yn1aminederivativesaspotentcysteinylleukotrienereceptorcyslt2antagonists AT belaloalnajjar synthesismoleculardockingandantiinflammatoryevaluationofnovel4benzod13dioxol5yloxynn2yn1aminederivativesaspotentcysteinylleukotrienereceptorcyslt2antagonists AT raedaalqawasmeh synthesismoleculardockingandantiinflammatoryevaluationofnovel4benzod13dioxol5yloxynn2yn1aminederivativesaspotentcysteinylleukotrienereceptorcyslt2antagonists |