Quercetin Derivatives from Bidens pilosa Suppressed Cell Proliferation via Inhibition of RSK2 Kinase and Aldose Reductase Enzymes: UPLC-MS/MS, GC-MS, In Vitro, and Computational Studies

Traditionally, Bidens pilosa L. is an edible herb utilized for various ailments. The study accomplished a complete analysis of B. pilosa extract including UPLC/T-TOF-MS/MS, GC-MS, and in vitro antiproliferative activity, in addition to molecular docking on kinase and aldose reductase enzymes. From GC-MS analysis, the percentage of identified unsaturated fatty acids (FAs) (11.38%) was greater than saturated FAs (8.69%), while the sterols percent (39.92%) was higher than the hydrocarbons percent (6.6%). Oleic and palmitic acids are the major FAs (9.48% and 6.14%, respectively). Phytochemical profile uncovered the presence of quercetin, kaempferol, myricetin, and isorhamnetin aglycones and/or glycoside derivatives alongside apigenin, acacetin, and luteolin derivatives. B. pilosa extract suppressed cell proliferation in a concentration-dependent manner against SNB-19 and SK-MEL-5 cell lines (IC₅₀ 1.66 ± 0.06 and 4.04 ± 0.14 mg/mL, respectively). These potentials aligned with the molecular docking results on aldose reductase and kinase enzymes with promising binding affinities (- 5.3 to - 8.89 kcal mol^-1). B. pilosa metabolites were found as kinases and aldose reductase inhibitors, which rationalize their antiproliferative activity. Unfortunately, toxicity assessments were not performed to assess the safety of B. pilosa extract. Assessment of the therapeutic efficiency via in vivo and clinical studies is required.