2. Academic Validation
  3. Discovery of deoxylimonin δ-lactam derivative with favorable anti-inflammation and antinociception efficacy from chemical modified limonin/deoxylimonin analogs

Discovery of deoxylimonin δ-lactam derivative with favorable anti-inflammation and antinociception efficacy from chemical modified limonin/deoxylimonin analogs

  • Bioorg Chem. 2020 Jul;100:103886. doi: 10.1016/j.bioorg.2020.103886.
Shaochi Wang 1,  Xueqing Han 1,  Yun Yang 2,  Chen Zhou 2,  Danmeng Luo 2,  Wensong He 2,  Qihua Zhu 3,  Yungen Xu 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
  • 2 Jiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 211198, China.
  • 3 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. Electronic address: zhuqihua@cpu.edu.cn.
  • 4 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. Electronic address: xyg@cpu.edu.cn.
PMID: 32371249 DOI: 10.1016/j.bioorg.2020.103886
Abstract

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 E2 formation.

Keywords

Anti-inflammation; Antinociception; Downregulate Prostaglandin E(2); Limonin derivative; Suppress Cyclooxygenase 2.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z