A New Cytotoxic Dimeric Sesquiterpene Isolated from Inula racemosa Hook. f. (Root): In Vitro and In Silico Analyses

A new dimeric sesquiterpene named disesquicin (compound 1) was isolated from Inula racemosa roots by normal-phase MPLC (Medium Pressure Liquid Chromatography), and its structure was established by using extensive spectral analysis. Compound 1, when tested on different human cancer cell lines, showed marked cytotoxic activity (IC50 (mu g/mL): 5.99 (MDA-MB), 9.10 (HeLa), and 12.47 (A549)). Docking study revealed that it binds at the catalytic domain of PLK-1 and interacts with catalytic site residues Leu59, Gly60, Lys61, Gly62, Cys67, Ala80, Lys82, Leu130, Arg136, Ser137, Leu139, Glu140, Lys178, Gly180, Asn181, Phe183, and Asp194. The binding of compound 1 to PLK-1 is spontaneous in nature as evident by a free energy of-8.930 kcal mol(-1), corresponding to a binding affinity of 3.54 x 10(6) M-1. Results showed that compound 1 exhibited cytotoxic potential that was further confirmed by in vivo investigations.

Automated summary

A new dimeric sesquiterpene compound, disesquicin (compound 1), isolated from Inula racemosa roots, exhibited significant cytotoxic activity against various human cancer cell lines. Docking study revealed its binding at the catalytic domain of PLK-1, indicating a potential mechanism for its cytotoxic effects. In vivo investigations further confirmed the cytotoxic potential of compound 1.