Design, Synthesis, and Anti-Hepatic Fibrosis Evaluation of Cordycepin Derivatives
Wenfang Pan, Siqi Liu, Yuanchen Zhong, Bixi Tang, Yi Zang, Yuanchao Xie
TL;DR
This study designs and tests cordycepin derivatives to find new anti-liver fibrosis compounds that inhibit cell activation and improve liver health.
Contribution
The study introduces cordycepin derivative 3a, which shows enhanced anti-fibrotic activity and activates the AMPK signaling pathway.
Findings
Compound 3a dose-dependently downregulates α-SMA and collagen-I at mRNA and protein levels.
Compound 3a inhibits LX-2 cell migration and shows improved metabolic stability in liver microsomes.
Compound 3a activates the AMPK signaling pathway, suggesting a potential mechanism for its anti-fibrotic effect.
Abstract
Activation of hepatic stellate cells (HSCs) featuring upregulated expression of α-smooth muscle actin (α-SMA) is recognized as a key driver for hepatic fibrosis, which provides a promising strategy for seeking anti-liver fibrogenic agents via suppressing the activation event. In this study, we designed and synthesized twenty-eight cordycepin derivatives through structural modifications at the C2 position and the C6-NH2 group of the purine moiety. These compounds were screened for their inhibitory effects on HSC activation by detecting the mRNA expression of α-SMA using quantitative real-time polymerase chain reaction (qPCR) in the LX-2 cell model. Most compounds displayed inhibitory activity comparable to cordycepin, with compound 3a bearing a C2-chloro and a N6-methyl-N6-(2-chlorobenzyl) substituent, demonstrating enhanced in vitro anti-fibrotic effect. This compound was able to…
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Taxonomy
TopicsLiver physiology and pathology · Liver Disease Diagnosis and Treatment · Bioactive Compounds in Plants