andrographolide has been researched along with Acute-Lung-Injury* in 2 studies
2 other study(ies) available for andrographolide and Acute-Lung-Injury
| Article | Year |
|---|---|
From irreversible to reversible covalent inhibitors: Harnessing the andrographolide scaffold for anti-inflammatory action.
Covalent drugs with prolonged actions often show superior potency, yet integrated strategies for optimizing their structural and electronic features are lacking. Herein, we present our effort directed towards understanding the contribution of chemical reactivity to biological potency to rationally design new covalent inhibitors based on the ent-ladane andrographolide scaffold for anti-inflammatory action. Specifically, a series of andrographolide derivatives comprising various Michael acceptors was developed and their thiol reactivity was assayed under various chemical and biological conditions. The cell-based SAR studies permitted the assessment of the inhibitor efficacy in more complex systems, which were often limited in traditional covalent drug development using isolated proteins or peptides. Our in vitro study identified enone 17 as the most promising candidate which demonstrated potent anti-inflammatory activity and superior safety profiles as compared to the lead compound andrographolide. Its reversibility following a Michael addition reaction with biological thiols resulted in more predictable pharmacological responses. In addition, 17 exhibited good in vivo efficacy at doses as low as 0.3 mg/kg when tested in LPS-induced acute lung injury model. Given a good balance of chemical reactivity and biological potency, enone 17 potentially offers a new therapeutic option based on natural product chemistry for the management of inflammatory conditions. Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Diterpenes; Drug Design; Mice; Sulfhydryl Compounds | 2020 |
Andrographolide derivative as STAT3 inhibitor that protects acute liver damage in mice.
Sustained activation of the Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway contributed to the progression of cancer and liver diseases. STAT3 signaling inhibitor has been extensively investigated for pharmacological use. We synthesized a series of andrographolide derivatives, and characterized their activity against STAT3 signaling pathway both in vitro and in the CCl Topics: Acute Lung Injury; Animals; Carbon Tetrachloride; Cells, Cultured; Diterpenes; Dose-Response Relationship, Drug; Humans; Male; Mice; Mice, Inbred BALB C; Molecular Structure; Protective Agents; Signal Transduction; STAT3 Transcription Factor; Structure-Activity Relationship | 2018 |