Discovery of PRMT5 Inhibitors from Semiliquidambar Cathayensis Chang Using Computational and Bioactivity Evaluation

Area of Science:

• Natural Product Chemistry
• Computational Chemistry
• Biochemistry

Background:

• Protein arginine methyltransferase 5 (PRMT5) is implicated in various diseases, including cancer.
• Inhibiting PRMT5 activity is a therapeutic strategy for disease management.

Purpose of the Study:

• To identify PRMT5 inhibitors from the chemical constituents of Semiliquidambar cathayensis Chang.
• To explore natural products as a source for novel therapeutic agents.

Main Methods:

• Literature review to identify 101 chemical constituents of S. cathayensis Chang.
• Molecular docking and PRMT5 enzyme assays to screen for inhibitors.
• Molecular dynamics simulations to analyze inhibitor-PRMT5 interactions.

Main Results:

• Two PRMT5 inhibitors, (+)-catechin (13.33 ± 2.84 μM) and quercetin (0.85 ± 0.24 μM), were identified.
• Key amino acid residues (PHE327, GLU435, TRP579) were found to be crucial for binding free energy.
• The study demonstrated an effective computational approach for rapid natural product drug discovery.

Conclusions:

• Quercetin and (+)-catechin show significant potential for further development as PRMT5 inhibitors.
• The integrated computational and bioactivity evaluation strategy is effective for discovering natural product-derived inhibitors.
• This approach aids in identifying active compounds from diverse natural product structures.