Comprehensive computational investigation of Aerva lanata phytoconstituents as potential HER2 kinase inhibitors for the treatment of cancer

Human epidermal growth factor receptor 2 (HER2) is a clinically significant
oncogenic kinase that drives tumor growth, survival, and therapeutic resistance,
making it a validated target for anticancer drug discovery. In the present study, an
integrated in silico strategy was employed to evaluate phytochemicals from Aerva
lanata as potential HER2 kinase inhibitors by combining ADMET profiling with
molecular docking analysis. Sixteen phytochemical constituents belonging to
alkaloids, flavonoids, and phenolic acids were selected based on reported
phytochemical evidence, structural diversity, and pharmacological relevance.
Physicochemical properties, drug-likeness, and pharmacokinetic parameters were
predicted using SwissADME and ADMETlab 3.0, revealing that most alkaloids
and aglycone flavonoids complied with Lipinski’s rule of five, exhibited molecular
weights below 500 Da, optimal lipophilicity (logP ~1–3), and acceptable safety
profiles. Molecular docking was performed against the HER2 kinase domain using
AutoDock Vina integrated in PyRx, followed by interaction analysis in Discovery
Studio. Docking results demonstrated binding energies ranging from −4.5 to −9.9
kcal/mol, with several phytochemicals outperforming the native ligand (−8.9
kcal/mol). Notably, apigenin 7-O-β-D-glucoside showed the strongest affinity
(−9.9 kcal/mol), followed by 10-methoxy-canthin-6-one (−9.1 kcal/mol), canthin-
6-one (−9.0 kcal/mol), and quercetin (−8.3 kcal/mol). These compounds formed
multiple hydrogen bonds (bond lengths ~2.0–2.8 Å) and hydrophobic interactions
with key catalytic residues such as MET801, LEU796, ASP863, and VAL734,
indicating stable ligand–protein complexes. Overall, this study highlights Aerva
lanata as a promising source of lead scaffolds for HER2-targeted anticancer therapy
and provides a strong computational rationale for further in vitro and in vivo
validation