Comprehensive analysis of Crotalaria willdenowiana DC.: GC-MS profiling, antioxidant and anticancer activities, molecular docking studies, and in silico ADME profiling.

UNLABELLED: This study examines the methanol extract (ME) of Crotalaria willdenowiana through preliminary phytochemical screening and GC-MS analysis to identify its phytochemical constituents. ADME prediction of these compounds was performed using SwissADME, and docking studies against various Breast Cancer (BC) receptors such as [Epidermal Growth Factor Receptor (EGFR), Human Epidermal Growth Factor Receptor 2 (HER2), Dihydrofolate Reductase (DHFR), and NUDIX hydrolase type 5 (NUDT5)] were conducted with Autodock 4.2.6. The extract's antioxidant activity was assessed using four methods (DPPH, TEAC, ORAC, and FRAP), and its anticancer effect on the MCF-7 cell line was examined. This study identified 11 promising phytochemicals from C. willdenowiana through GC-MS analysis. All compounds demonstrated favorable drug-like and pharmacokinetic properties, adhering to Lipinski's Rule of Five. Molecular docking studies indicated strong binding affinities toward EGFR, HER2, DHFR, and NUDT5, notably for compounds, such as Acrylophenone, 3,3-diphenyl-semicarbazone, 2-(acetoxymethyl)-3-(methoxycarbonyl) biphenylene, and N-(2-acetylcyclopentylidene) cyclohexylamine. Additionally, in vitro assays showed that the methanolic extract (ME) of C. willdenowiana exhibited significant antioxidant (DPPH 158.61 µgTE/g; ORAC 111.31 μmolTE/g; FRAP 159.73 µgTE/g; and TEAC 193.80 μmolTE/g) and anticancer activities, with an IC₅₀ of 174.80 μg/ml in the anticancer assay. These results support the potential of C. willdenowiana as a source for innovative herbal remedies and pharmaceutical agents to combat various diseases.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-025-04409-z.