Department of Chemistry & Physics, Augusta University, Augusta, GA 30912, USA; Department of Pharmaceutical Organic Chemistry Faculty of Pharmacy, Zagazig University, 44519 Zagazig, Egypt.
Department of Pesticide Chemistry, National Research Centre, Dokki, Giza 12622, Egypt.
Bioorg Chem. 2022 Feb;119:105557. doi: 10.1016/j.bioorg.2021.105557. Epub 2021 Dec 14.
A new set of ibuprofen-quinoline conjugates comprising quinolinyl heterocycle and ibuprofen moieties linked by an alkyl chain were synthesized in good yields utilizing an optimized reaction procedure in a molecular hybridization approach to overcome the drawbacks of the current non-steroidal anti-inflammatory drugs. The synthesized conjugates were screened for their anti-inflammatory, and ulcerogenic properties. Several conjugates were found to have significant anti-inflammatory properties in the carrageenan-induced rat paw edema test without showing any ulcerogenic liability. In addition, most conjugates showed promising peripheral analgesic activity in the acetic acid-induced writhing test as well as central analgesic properties in the in vivo hot plate test. The most promising conjugates were the unsubstituted and 6-substituted fluoro- and chloro-derivatives of 2-(trifluoromethyl)quinoline linked to ibuprofen by a propyl chain. Their anti-inflammatory activity was evaluated against LPS-stimulated inflammatory reactions in RAW264.7 mouse macrophages. In this regard, it was found that most of the conjugates were able to significantly reduce the release and production of nitric oxide in the LPS-stimulated macrophages. The secretion and expression of the pro-inflammatory cytokines IL-6, TNF-α, and inducible nitric oxide synthase (iNOS) were also significantly suppressed.
一组新的布洛芬-喹啉缀合物由喹啉杂环和布洛芬部分通过烷基链连接组成，采用优化的反应程序，以分子杂交的方法合成，以克服当前非甾体抗炎药物的缺点。合成的缀合物进行了抗炎和致溃疡特性的筛选。在角叉菜胶诱导的大鼠足肿胀试验中，发现几种缀合物具有显著的抗炎作用，而没有表现出任何致溃疡的倾向。此外，大多数缀合物在醋酸诱导的扭体试验中表现出有希望的外周镇痛活性，并且在体内热板试验中表现出中枢镇痛特性。最有前途的缀合物是未取代的和 6-取代的氟代和氯代 2-（三氟甲基）喹啉与通过丙基链连接的布洛芬的缀合物。它们的抗炎活性在 LPS 刺激的 RAW264.7 小鼠巨噬细胞炎症反应中进行了评估。在这方面，发现大多数缀合物能够显著降低 LPS 刺激的巨噬细胞中一氧化氮的释放和产生。促炎细胞因子 IL-6、TNF-α 和诱导型一氧化氮合酶（iNOS）的分泌和表达也被显著抑制。
