Design, green synthesis, Z/E(C=C)-isomerization, in silico molecular docking and ADME studies of some new lawsone enaminones as potential anti-breast cancer agents targeting HER2

A green, one-pot synthesis of some new 3-(arylamino)methylene)naphthalene-1,2,4(3H)-trione derivatives via a three-component reaction of lawsone, aromatic amines, and glyoxylic acid monohydrate in refluxing ethanol is reported. The reaction proceeds through a sequence of Knoevenagel condensation, Michael addition, cyclization and carbon monoxide extrusion. 1 H NMR spectroscopic analysis revealed that the lawsone enaminones exist predominantly in the keto-enamine tautomeric form and undergo Z/ E -isomerization about the C C bond in DMSO‑ d 6 at room temperature. Moreover, molecular docking against HER2 revealed that compounds 4b , 4e , and 4 f exhibited strong binding affinities (−10.4 to −10.6 kcal/mol), supported by key hydrogen bonds (3.01–3.24 Å) and hydrophobic interactions. The RMSD values for compounds 4a-i stabilized near 0.00 by the end of the simulation, indicating the formation of stable protein-ligand complex. Furthermore, ADME, pharmacokinetic, and drug-likeness analyses showed that these compounds possess favorable drug-like properties and comply with Lipinski's rule of five, supporting their potential as HER2 inhibitors. • A green synthesis of some new 3-(arylamino)methylene)naphthalene-1,2,4(3 H )-trione derivatives . • lawsone enaminones exist in the keto-enamine tautomeric form and undergo Z / E -isomerization in DMSO‑ d 6 at room temperature. • Analysis of Z/E isomer ratios using 1 H NMR spectra. • Molecular docking and ADME analyses were conducted to evaluate the binding interactions of the synthesized compounds with HER2. • Compounds 4b , 4e , and 4 f demonstrated potent HER2 binding affinity, making them promising candidates for anticancer activity.