Antiproliferative Activity and Molecular Docking Analyses of Sesquiterpene Lactones Obtained from Activity-Directed Isolation of Centaurea saligna (K.Koch) Wagenitz in Neoplastic Cells.

Secondary metabolites obtained from plants are among the most commonly encountered chemotherapeutics used in cancer treatment. Plants contain thousands of metabolites; therefore, it is important to reach the compound primarily responsible for activity by fractionating plant extracts through activity-guided isolation. The cytotoxic activities of C. saligna fractions, sub-fractions, and all pure compounds obtained from the plant were investigated in vitro using MCF-7 (human breast cancer), HeLa (human cervical cancer), and PC-3 (prostate cancer) cell lines. Eighteen compounds were isolated from C. saligna, comprising eight sesquiterpene lactones, three flavonoids, five lignans, and two phenolic compounds, with their structures elucidated through ¹H-NMR, ¹³C-NMR, and HMBC spectroscopic techniques. The molecular docking scores of the pure compounds obtained from these sub-fractions were determined using both AutoDock and AutoDock Vina programs. It has been proven that the affinities of linichlorin B and aguerin B for Bcl-2 are higher than those of other compounds, considering the calculated Ki values and placement scores. Notable activities of linichlorin B, cynaropicrin, and aguerin B (with IC₅₀ values of 13.67 μg/ml, 6.79 μg/ml, and 3.46 μg/ml, respectively) were detected in the PC-3 cell line; aguerin B demonstrated activity most comparable to the standard anticancer agent doxorubicin. Likewise, linichlorin B, aguerin B, and cynaropicrin demonstrated notable efficacy in the HeLa and MCF-7 cell lines, as reported by the American National Cancer Institute. Aguerin B, linichlorin B, and cynaropicrin are projected to serve as promising novel chemotherapeutic agents for cancer therapy.