State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
Jiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 211198, China.
Bioorg Chem. 2020 Jul;100:103886. doi: 10.1016/j.bioorg.2020.103886. Epub 2020 Apr 24.
Chemical modifications on the A ring of limonin (1) and deoxylimonin (2) afforded 28 structural characterized derivatives, which were firstly subjected to preliminary in vivo analgesic and anti-inflammatory screen by mice model. The most promising candidate, deoxylimonin analog II-B-2 (70 mg/kg) with 3,4-dimethoxyphenylethyl moiety substitued δ-lactam in the A ring, exhibited better analgesic activity than aspirin (200 mg/kg) and stronger anti-inflammatory efficacy than naproxen (150 mg/kg). Further in vivo evaluation confirmed its advantage over limonin and showed dose-response dependent manner, and follow-up research suggested that the anti-inflammatory effect of compound II-B-2 may be attributed to the downregulation of cyclooxygenase 2 expression and the suppression of prostaglandin E formation.
对柠烯（1）和去氧柠烯（2）的 A 环进行化学修饰，得到了 28 种结构特征明确的衍生物，这些衍生物首先通过小鼠模型进行了初步的体内镇痛和抗炎筛选。最有前途的候选物是去氧柠烯类似物 II-B-2（70mg/kg），其 A 环中的δ-内酰胺取代了 3,4-二甲氧基苯乙基部分，其镇痛活性优于阿司匹林（200mg/kg），抗炎效果强于萘普生（150mg/kg）。进一步的体内评价证实了它优于柠烯，并表现出剂量依赖性，后续研究表明，化合物 II-B-2 的抗炎作用可能归因于环氧化酶 2 表达的下调和前列腺素 E 形成的抑制。
