Unknown

Dataset Information

0

Structure-Activity Relationship of Aloperine Derivatives as New Anti-Liver Fibrogenic Agents.

ABSTRACT: Twenty-seven novel 12N-substituted aloperine derivatives were synthesized and investigated for their inhibitory effects on collagen ?1 (I) (COL1A1) promotor in human hepatic stellate LX-2 cells, taking aloperine (1) as the hit. A structure-activity relationship (SAR) study disclosed that the introduction of suitable substituents on the 12N atom might enhance the activity. Compound 4p exhibited a good promise on down-regulating COL1A1 expression with the IC50 value of 16.5 ?M. Its inhibitory activity against COL1A1 was further confirmed on both mRNA and protein levels. Meanwhile, it effectively inhibited the expression of other fibrogenic proteins, such as transforming growth factor ?1 (TGF-?1) and smooth muscle actin (?-SMA). It also exhibited good in vivo safety profile with the oral LD50 value of 400 mg kg-1 in mice. The results initiated the anti-liver fibrogenic study of aloperine derivatives, and the key compound 4p was selected as a novel lead for further investigation against liver fibrogenesis.

SUBMITTER: Wang K 

PROVIDER: S-EPMC7663597 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Structure-Activity Relationship of Aloperine Derivatives as New Anti-Liver Fibrogenic Agents.

Wang Kun K   Guo Zhihao Z   Bao Yunyang Y   Pang Yudong Y   Li Yinghong Y   He Hongwei H   Song Danqing D  

Molecules (Basel, Switzerland) 20201027 21

Twenty-seven novel 12<i>N</i>-substituted aloperine derivatives were synthesized and investigated for their inhibitory effects on collagen α1 (I) (COL1A1) promotor in human hepatic stellate LX-2 cells, taking aloperine (<b>1</b>) as the hit. A structure-activity relationship (SAR) study disclosed that the introduction of suitable substituents on the 12<i>N</i> atom might enhance the activity. Compound <b>4p</b> exhibited a good promise on down-regulating COL1A1 expression with the IC<sub>50</sub  ...[more]

Similar Datasets

Unknown Structure-activity relationship studies of lipophilic teicoplanin pseudoaglycon derivatives as new anti-influenza virus agents.
| S-EPMC7115582 | biostudies-literature
Unknown The structure-activity relationship of urea derivatives as anti-tuberculosis agents.
| S-EPMC3176295 | biostudies-literature
Unknown Synthesis and Structure-Activity Relationship of Pyxinol Derivatives as Novel Anti-Inflammatory Agents.
| S-EPMC7153010 | biostudies-literature
Unknown Discovery and structure activity relationship of glyoxamide derivatives as anti-hepatitis B virus agents.
| S-EPMC7856252 | biostudies-literature
Unknown Quantitative structure-activity relationship (QSAR) and molecular docking of xanthone derivatives as anti-tuberculosis agents.
| S-EPMC7695880 | biostudies-literature
Unknown Structure-activity relationship of new anti-tuberculosis agents derived from oxazoline and oxazole benzyl esters.
| S-EPMC2843756 | biostudies-literature
Unknown Synthesis and Structure-Activity Relationship of Daphnetin Derivatives as Potent Antioxidant Agents.
| S-EPMC6222747 | biostudies-literature
Unknown Cinnamic Derivatives as Antitubercular Agents: Characterization by Quantitative Structure-Activity Relationship Studies.
| S-EPMC7037561 | biostudies-literature
Unknown Anti-dengue-virus activity and structure-activity relationship studies of lycorine derivatives.
| S-EPMC7162318 | biostudies-literature
Unknown Anti-cancer efficacy of silybin derivatives -- a structure-activity relationship.
| S-EPMC3610875 | biostudies-other