Bioactivity and molecular docking of lactones isolated from Czerep.

Two cytotoxic sesquiterpene lactones, 17-epichlorohyssopifolin A () and chlorjanerin (), and a monoterpene lactone, loliolide () were isolated from . The cytotoxicity of the total extract and terpenoids - were evaluated against three human cancer cells (HepG2, PC-3, and HT-29), along with the human normal primary epidermal keratinocytes (HEKa) cells. With IC values ranging between 0.6 ± 0.04 and 5.0 ± 0.61 μg/mL against HepG2; 0.2 ± 0.01 and 11.9 ± 1.31 μg/mL against PC-3, and 0.04 ± 0.013 and 8.9 ± 0.97 μg/mL against HT-29, the total extract, and lactones - demonstrated cytotoxic effects. Compound displayed the strongest impact on all cancer cells and a slightly safe effect on the normal cells HEKa. Compound caused accumulation of HepG2 and HT-29 cells in G1 phase as displayed cell cycle analysis. On the other hand, the cell distributions were increased in the S phase in PC-3 cells. Furthermore, caused apoptosis in PC-3 and HePG2 cells with 91.50%, and 79.72 %, respectively. A higher fraction of necrotic cells was observed in HT-29 cells amounting to 23.60%. These results suggested that the promising cytotoxicity exhibited by is brought by the apoptosis induction in the cancer cells, which were evaluated. As the compounds showed antiproliferative effect against the HT-29 cells, the docking simulation was performed aiming at determining how they would interact with the EGFR enzyme, whose PDB: 4I23 is considered one of the two distinct wild types of EGFR enzymes. The antibacterial activity results revealed that showed the most remarkable antibacterial effects, especially against the examined Gram-positive bacteria. The total extract exhibited potent activity against all examined bacteria. The total extract showed a potent antifungal effect against two and two pathogens. The antioxidant activity revealed the potency of the total extract and as antioxidant candidates. The obtained results refer to the importance of as a source of potent antiproliferative agents and the whole plant as an antipathogenic and antioxidant agent.