Metabolomic Profiling and Cytotoxic Activity of Launaea nudicaulis : Molecular Docking with Topoisomerases

Launaea nudicaulis (L.) Hook. f., Asteraceae, is a wild plant growing in Egypt, used traditionally for treatment of many diseases. LC-HRMS analysis of different polarity soluble extracts allowed the annotation of fifteen compounds: three alkaloids, four flavonoids, three phenolic acids, three coumarins, one sphingolipid, and one triterpene. Chemical investigation led to isolation and identification of caffeic acid, luteolin, luteolin7- O -glucoside, lupeol, β-sitosterol, and palmitic acid. Cytotoxic evaluation for hexane, CH 2 Cl 2 , ethyl acetate, and n -butanol extracts using MTT assay against three cancer cell lines HL-60, HT-29, and MCF-7 showed a remarkable cytotoxic activity for the CH 2 Cl 2 -soluble extract against HL-60 and HT-29 with IC 50 5.8 and 8.26 µg/ml, respectively, as well the n -butanol extract showed good activity against HL-60 and HT-29 with IC 50 11.6 and 9.6 µg/ml, respectively. Docking study was performed on topoisomerase enzymes (I, IIα, and IIβ) and provided a rationale for the biological outcomes where three natural compounds in the plant strongly bound to the proteins, particularly, luteolin-7-(6″-malonylneohesperidoside) with binding affinities of − 11.341, − 10.866, and − 10.111 kcal/mol, respectively, and kaempferol-3- O -[6″-malonyl-β- d -apiofuranosyl-(1 → 2)-β- d -glucopyranoside] with binding affinities of − 10.796, − 10.102, and − 9.916 kcal/mol, respectively. Also, luteolin-7- O -β- d -glucopyranoside docked with higher binding affinity to topoisomerase I (− 10.367 kcal/mol) compared to topoisomerases IIα and IIβ. Graphical Abstract