Licochalcone A as a potential anti-Toxoplasma agent.
Licochalcone A as a Potential Anti-Agent: A Target Identification and Pharmacokinetic Study.
AI Summary
Key Findings
Abstract
Toxoplasmosis is a zoonotic disease with limited therapeutic options, which are further hampered by significant toxicity and suboptimal efficacy. Effective interventions for chronic infection remain insufficient, and thus, natural product-derived drug screening remains a key focus in anti-research. Licochalcone A (Lico A), a major bioactive compound isolated from, exhibits potent activity againsttachyzoites. However, systematic studies of its targets, pharmacokinetics, and efficacy are lacking, hindering its development as an anti-candidate drug. In this study, we used SPR-MS to identify 33 high-affinity target proteins (affinity score>1000). Furthermore, an AI-driven multidimensional analysis identified a cluster of five proteins (MORN1, D3XD37, ABCB2, MIC15, and IDH), withMORN1 yielding the highest composite score. RNAi experiments confirmedMORN1 as a key target, as its silencing attenuated the anti-proliferative effect of Lico A. Western blotting, NanoDSF, and SPR supported direct binding between Lico A andMORN1, suggesting that Lico A modulatesMORN1 thermal stability through residues S168 and D203, with high species specificity. Pharmacokinetic evaluation revealed that Lico A had favorable absorption and blood-brain barrier permeability, supporting its potential utility in treating brain disease. In vitro assays showed that Lico A effectively inhibitedbrain cyst formation. Collectively, these findings support Lico A as a promising candidate for the treatment of toxoplasmosis.
Affiliation
Bing Li
External References
- PubMed ID:
- 41897346
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