Abstract
A germacranolide (1) together with four guaianolide sesquiterpenes (2 - 5) were isolated from Reichardia tingitana, with the first report on the separation of compounds 1 - 4 from this plant. Their structures were identified as, 3β-hydroxybalchanolide (1), 15-desacetylmatricarin-8-O-β-d-glucopyranoside (2), 11β, 13-dihydro-lactucin (3), cichorioside G (4), and 15-desoxylactucin-α-d-glucopyranoside (5), based on the analysis of 1D and 2D NMR spectral data, HRESIMS and comparison with literature. Molecular docking studies were performed to examine the proposed apoptotic activity of the five naturally isolated sesquiterpenes against Mcl-1. The isolated compounds were tested for their cytotoxic activities against different cancer cell lines compared to doxorubicin as a reference standard. The results showed that compound (4) and compound (2) have the highest cytotoxicity. These two active compounds were further evaluated by cell cycle analysis and Annexin V-FITC (Anx V) apoptosis assay as well. Compounds (4 and 2) halted the cell cycle at sub G1, S, and G2/M phases with 9.18-fold, 2.59-fold, 14.8-fold, 2.48-fold, 6.33-fold, 15.71-fold, respectively, compared to that of the control. Moreover, compounds (4 and 2) arrested the cell cycle mostly at G2/M phase (14.8-fold and 15.71-fold, respectively), indicating a very similar mechanism of action and promising high antitumor activities for both isolates. Furthermore, both compounds (4 and 2) showed a marked increase in the AnxV-FITC apoptotic cells% in the late phase (from 0.00 to 2.80%, and from 0.00 to 12.65%), respectively, compared to the control.
[Display omitted]
•A germacranolide (1) together with four guaianolide sesquiterpenes (2 - 5) were isolated from reichardia tingitana, with the first report on the separation of compounds 1 - 4 from this plant.•The isolated compounds were tested for their cytotoxic activities against different cancer cell lines compared to doxorubicin as a reference standard. The results showed that compound (4) and compound (2) have the highest cytotoxicity.•These two active compounds were further evaluated by cell cycle analysis and annexin V-FITC (Anx V) apoptosis assay as well. Compounds (4 and 2) halted the cell cycle at sub G1, S, and G2/M phases with 9.18-fold, 2.59-fold, 14.8-fold, 2.48-fold, 6.33-fold, 15.71-fold, respectively, compared to that of the control.