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...

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Bibliographic Details
Main Authors: Areej M. Jaber, Mohammed M. Al-Mahadeen, Belal O. Al-Najjar, Raed A. Al-Qawasmeh
Format: Article
Language:English
Published: Pensoft Publishers 2025-02-01
Series:Pharmacia
Online Access:https://pharmacia.pensoft.net/article/143171/download/pdf/
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Summary: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:
ISSN:2603-557X