Rational design, synthesis and anti-inflammatory activity of 6-substituted dihydrobenzophenanthridine derivatives

被引：0

作者：

Huang, Lei ^{[1
,2
]}

Liu, Wei ^{[1
,2
]}

Lv, Xinye ^{[1
,2
]}

Ge, Xiaomei ^{[1
,2
]}

He, Zhehao ^{[1
,2
]}

Yang, Yingxue ^{[1
,2
]}

Tang, Yuhui ^{[1
,2
]}

Wang, Lin ^{[1
,2
]}

Zeng, Jianguo ^{[1
,2
]}

Cheng, Pi ^{[1
,2
]}

机构：

[1] Hunan Agr Univ, Hunan Key Lab Tradit Chinese Vet Med, Changsha 410128, Hunan, Peoples R China

[2] Chinese Med Mat Breeding Innovat Ctr, Yuelushan Lab, Changsha 410128, Hunan, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2025年 / 122卷

关键词：

Dihydrobenzophenanthridine; Derivatives; Synthesis; Anti-inflammatory; KAPPA-B; INFLAMMATION; MEDIATORS; ROLES;

D O I：

10.1016/j.bmc.2025.118145

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

a series of 6-substituted dihydrobenzophenanthridine alkaloids were synthesized by introduction of different functional groups to C-6 of dihydrobenzophenanthridine backbone. The preliminary anti-inflammatory activities of all compounds were screened by investigating the inhibitory ability on NO production in LPS-stimulated RAW 264.7 cells. Among synthesized compounds, 6-(N-phenyl)-aminocarbonyl methyl dihydrochelerythrine (compound 12b) showed increased anti-inflammatory ability and decreased cytotoxicity and could inhibit the expression of pro-inflammatory factors TNF-alpha and IL-6 in RAW 264.7 macrophages. The anti-inflammatory ability of compound 12b was further evaluated using DSS-induced mice colitis models based on colonic tissue damage assessment, histopathological assessment and immunohistochemical analysis. In vivo experiment revealed that compound 12b had good alleviating effect on acute colitis in mice. In conclusion, compound 12b may be a promising anti-inflammatory lead compound.

引用

页数：10

共 24 条

[1] Mechanisms of the systemic inflammatory response [J].