Cytotoxicity and molecular docking analysis of racemolactone I, a new sesquiterpene lactone isolated from .

Context: Traditionally, Hook. f. (Asteraceae) has been reported to be effective in cancer treatment which motivated the authors to explore the plant for novel anticancer compounds.

Objective: To isolate and characterize new cytotoxic phytoconstituents from roots.

Materials And Methods: The column chromatography of ethyl acetate extract furnished a novel sesquiterpene lactone whose structure was established by NMR (1D/2D), ES-MS and its cytotoxic properties were assessed on HeLa, MDAMB-231, and A549 cell lines using MTT and LDH (lactate dehydrogenase) assays. Further, morphological changes were analyzed by flow cytometry, mitochondrial membrane potential, AO-EtBr dual staining, and comet assay. Molecular docking and simulation were performed using Glide and Desmond softwares, respectively, to validate the mechanism of action.

Results: The isolated compound was identified as racemolactone I (compound ). Amongst the cell lines tested, considerable changes were observed in HeLa cells. Compound (IC = 0.9 µg/mL) significantly decreased cell viability (82%) concomitantly with high LDH release (76%) at 15 µg/mL. Diverse morphological alterations along with significant increase (9.23%) in apoptotic cells and decrease in viable cells were observed. AO-EtBr dual staining also confirmed the presence of 20% apoptotic cells. A gradual decrease in mitochondrial membrane potential was observed. HeLa cells showed significantly increased comet tail length (48.4 µm), indicating broken DNA strands. studies exhibited that compound binds to the active site of Polo-like kinase-1 and forms a stable complex.

Conclusions: Racemolactone I was identified as potential anticancer agent, which can further be confirmed by investigations.