Phytochemical screening of Onopordum acaulon and in silico evaluation of its potential interactions with Heat Shock Protein 90 (HSP90) and druglikeness

Abstract

Heat Shock Protein 90 (HSP90) is a key molecular chaperone involved in cancer progression and represents an important therapeutic target. Additionally, plant-derived metabolites have garnered increasing attention due to their diverse biological activities. Previous studies on Onopordum acaulon have demonstrated its potential in the green synthesis of zinc oxide nanoparticles, which exhibit notable antimicrobial and biological properties, highlighting its richness in bioactive compounds. This investigation, which robustly combines phytochemical screening with computational methods, offers a strong strategy for identifying bioactive plant metabolites. The aerial parts (leaves, flowers, and edible seeds) of Onopordum acaulon were investigated using various solvents, including ethanol, water, and ethanol–water mixtures, for extraction. The phytochemical screening revealed the presence of flavonoids, tannins, anthocyanins, and alkaloids in varying amounts. Quantitative analysis showed that flowers had the highest total phenolic (TPC) and flavonoid contents (TFC), especially with 60-90% ethanol, while anthocyanins peaked in 10% ethanol flower extracts and alkaloids in 60-90% ethanol flower and seed extracts. The hydroethanolic flower extract (2:8, ethanol: water) showed the highest total tannin content (TTC) value (143.87 ± 1.66 mg CE/g). These findings confirm that both the plant organ and the solvent polarity influence extraction efficiency. Furthermore, an in silico evaluation explored the anticancer potential of key phytochemicals against HSP90. Molecular docking indicated that Apigenin, Luteolin, and Hispidulin had stronger binding affinities (-7.272 to -6.924 kcal/mol) than the reference inhibitor, forming multiple stabilizing interactions with critical residues. ADMET profiling predicted favorable oral bioavailability and low toxicity for most compounds. Molecular dynamics simulations (MDS) confirmed the stability of Hispidulin and Luteolin complexes, while MM-PBSA free energy analysis revealed that Apigenin exhibited the strongest binding affinity (ΔTOTAL= -22.61 kcal/mol). These integrated experimental and computational results underscore O. acaulon as a promising source of phenolics and alkaloids, instilling hope for the future of drug development in the field of pharmacology and botany.