Researchers modified dimethyl cardamonin into derivatives 2a and 2b and evaluated them in lung-cancer cells, docking and molecular dynamics. Both inhibited NCI-H460 cells at IC50 values near 8 micromolar and were less toxic to MRC-5 cells than osimertinib in this assay, but direct EGFR-mediated action was not demonstrated.
Key findings
- In NCI-H460 cells, IC50 values were 7.97±0.62 and 7.91±2.77 micromolar for 2a and 2b, with weaker activity in A549. MRC-5 IC50 values were at least 50 for 2a and 16.08 for 2b, versus 3.43 micromolar for osimertinib. Docking and MM/GBSA supported computational binding but did not directly measure EGFR enzyme inhibition.
Why this matters globally
The structures may provide a starting point for improving chalcone potency and selectivity by linking synthetic chemistry with long simulations, but target validation and pharmacology are needed before therapeutic relevance can be claimed.
Thai researcher contribution
The Chiang Mai, Naresuan and Khon Kaen collaboration integrated natural-product chemistry, cell biology and computation to develop regional bioresource-derived leads.
Limitations to consider
MTT measures cell viability rather than mechanism. Direct EGFR enzyme or signalling assays, animal studies, pharmacokinetics and systemic toxicity were absent, and 2b had a limited MRC-5 selectivity margin. Docking is not evidence of binding in vivo.
Verify the original sources
International Journal of Molecular SciencesRead the original article↗DOI: 10.3390/ijms27146104