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

Abstract

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 (IC 50= 3.83 ± 0.2, 5.48 ± 0.3, 10.1 ±0.6 µg/ml respectively). Damsin has significant COX-2 inhibitory activity (IC 50 33.97 ± 1.62 µg/ml) while hymenin showed highest selectivity to COX-1 (IC 50 = 18.21 µg/ml) and significant inhibition of NO (IC 50 18.19 ± 0.75 µg/ml). From docking study, maritimolide showed higher affinity towards human Src kinase than 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 α-methylene-γ-lactone moiety enhances the activity against tested cell lines, OH group at C-1 increase activity of hymenin. However; the reduction of the double bond at C-2 as in damsin resulted in significant decrease in activity against HCT-116 and MCF-7 cells.

Preliminary Phytochemical and Biological Evaluation of Rudbeckia hirta Flowers

“…In addition, rudbeckolide (168), one of the major sesquiterpenoids identified in the studied methanolic extract, showed strong inhibitory activity in vitro against the pro-inflammatory enzyme 5-LOX [17]. The literature suggests that pseudoguaianolidetype lactones showed potent cytotoxic activity against breast cancer cells in vitro [77][78][79][80][81]. Qin et al, 2013 [77] described selective cytotoxicity towards the MCF-7 and MDA-MB-231 cell lines by monoacetylated pseudoguaianolides (bigelovin and 2α-acetoxy-4β-hydroxy-1αH,10αH-pseudoguai-11(13)-en-12,8β-olide) isolated from Inula lineariifolia Turcz (Asteraceae).…”

“…Another monoacetylated lactone (aucherinolide) isolated from Inula aucheriana DC demonstrated high cytotoxicity against MCF-7 [78]. Non-acetylated form of pseudoguaianolides (hymenin, ambrosin, damsin) isolated from Ambrosia maritima L. (Asteraceae) showed moderate toxicity to MCF-7 [80]. The series of twenty-one 10α-methylpseudoguaianolides (helenanolide-type) and their esters isolated from Arnica species (Asteraceae) were tested in vitro against the cloned Ehrlich ascites tumor cell line, EN2 [79].…”

In vitro and in vivo bioactivities of Ambrosia maritima and Bituminaria bituminosa organic extracts from Algeria

“…This finding is similar to the results of Said et al [33], who demonstrated the richness of A. maritima in terms of flavonoids. In addition to these metabolites, A. maritima includes a variety of other secondary metabolites, such as pseudoguaianolide sesquiterpene lactones, coumarins, triterpenes, sterols, and sesquiterpene lactones [12]. Phenolic acids and flavonoids play a preventive role in the development of some cancers and chronic diseases.…”

“…Accordingly, many flavonoid-rich plants demonstrate anti-inflammatory effect by exhibiting an anti-denaturation capacity [38][39][40][41][42]. Previous studies have also discussed the anti-inflammatory effects of both A. maritima and B. bituminosa, in relation to their phytochemical profile [12,43].…”

“…The phytochemical composition of A. maritima includes a variety of secondary metabolites, such as pseudoguaianolides, sesquiterpene lactones, coumarins, triterpenes, and sterols. Sesquiterpene lactones have diverse bioactivities, including antiinflammatory, antimicrobial, antitumor and antispasmodic properties [12].…”