Docking studies of sesquiterpene lactones isolated from Ambrosia maritima L. reveals their potential anti-inflammatory and cytotoxic activities

Five sesquiterpene lactones were isolated and identified from Ambrosia maritima L. Hymenin showed highest cytotoxic activity against HCT-116, A-549, and MCF-7 cell lines (IC50= 3.83 +/- 0.2, 5.48 +/- 0.3, 10.1 +/- 0.6 mu g/mL, respectively). Damsin has significant COX-2 inhibitory activity (IC50=33.97 +/- 1.62 mu g/mL) while hymenin showed highest selectivity to COX-1 (IC50 = 18.21 mu g/mL) and significant inhibition of NO (IC50=18.19 +/- 0.75 mu g/mL). The docking study revealed nice fitting into COX-1/2 and a higher binding affinity for maritimolide towards human Src kinase compared to the native ligand, Bosutinib. Results suggested that both COXs/Src kinase inhibition could contribute even partially to the overall mechanism of cytotoxic activity of the five compounds. The structure-activity relationship revealed that alpha-methylene-gamma-lactone moiety enhances the cytotoxic activity, OH group at C-1 increase activity of hymenin. However, the reduction of the double bond at C-2 as in damsin resulted in a significant decrease in activity against HCT-116 and MCF-7 cells.

Automated summary

Five sesquiterpene lactones were isolated from Ambrosia maritima L., among which hymenin showed the highest cytotoxic activity against various cancer cell lines. Hymenin also exhibited high selectivity to COX-1 and significant inhibition of NO. The structure-activity relationship study revealed the importance of alpha-methylene-gamma-lactone moiety and the presence of an OH group at C-1 in enhancing the cytotoxic activity.