Flavonoid glycosides of Stachys kurdica Boiss. & Hohen. against human lung cancer cells upon enzymatic docking paradigm

Genus Stachys with high polymorphic features has been considered for phytochemical evaluation of one species, Stachys kurdica with the specific habitat growing in the water and salinity stresses. Soxhlet apparatus was used to solvent-extract the aerial parts of S. kurdica and determine the structure of the purified compounds by NMR spectra. MTT assay was carried out in A549 cancer cells and human umbilical vein endothelial cells (HUVECs) for evaluating cytotoxicity of the S. kurdica. Besides, the in vitro antioxidant activity together with total phenolics and flavonoids content of the methanol extract was calculated. The inhibition affinity of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor-2 (VEGFR-2) enzymes of the purified compounds was performed using in silico molecular docking technique. Accordingly, two flavonoids: 1: scutellarein7-O-β-[6″-(acetyl)]glucoside and 2: acacetin7-[6″(apiosyl)-2″(acetyl)]-glucoside), were isolated and identified from S. kurdica. The results of MTT bioassay illustrated S. kurdica methanol extract had cytotoxic effects on A549 cancer cells with an IC₅₀ value of 216.03 µg/mL. Also, the results of the antioxidant assay indicated that the observed antioxidant activity of this plant was related to the presence of various polyphenolic compounds, including S. kurdica flavonoids. Overall, the phytochemical analysis of S. kurdica methanol extract revealed the presence of two acetylated acacetin and scutellarein derivatives for the first time in genus Stachys. Likewise, the ligand–receptor binding study indicated that compound 1 had the highest affinity with a docking score comparable to standard ligands on the target enzymes.