Antiproliferative activity of cardenolides on cell line A549: structure-activity relationship analysis.

Since the beginning, natural products have represented an important source of bioactive molecules for cancer treatment. Among them, cardenolides attract the attention of different research groups due to their cardiotonic and antitumor activity. The observed biological activity is closely related to their Na+/K+-ATPase inhibition potency. Currently, the discovery of new compounds against cancer is an urgent need in modern pharmaceutical research. Thus, the aim of this work is to determine the physicochemical properties and substituent effects that module the antiproliferative activity of cardenolides on the human lung cancer cell line A549. We build and curate a library with results obtained from literature; molecular descriptors were calculated in PaDEL software, and SAR/QSAR analysis was performed. The SAR results showed that cardenolides were sensitive to modifications in C and D steroidal ring and required substituent groups with the function of hydrogen bond acceptor at the C3 position. QSAR models to doubly linked-type cardenolides indicated that properties as lipoaffinity and atoms with the capacity to be hydrogen bond acceptors are involved in the increment of antiproliferative activity on A549 cell line. In contrast, the presence and position of very electro-negative atoms on the molecule decreased the antiproliferative effect on A549 cells. These results suggest that the antiproliferative capacity of cardenolides on the cell line A549 is strongly related to substituent groups on the C3 position, which must not be carbohydrate. Additionally, the steroidal rings C and D must remain without modifications.

Antiproliferative activity of spinasterol isolated of Stegnosperma halimifolium (Benth, 1844).

Cancer is the major cause of death in the world, representing a significant public health problem. Plants have been shown as a great source of secondary metabolites with anticancer activity. The aim of this work was evaluated the antiproliferative activity of the methanolic extracts, chemical fractions and the compound spinasterol isolated of medicinal plant Stegnosperma halimifolium. The methanolic extracts of stem, leaf and stem/leaf was obtained by maceration. The methanolic extract of stem was purified by successive extractions with solvents as n-hexane, ethyl acetate and ethanol. The n-hexane fraction was separated by column chromatographic and monitored by thin layer chromatographic. The compound spinasterol was characterized by 1H NMR, 13C NMR and Mass Spectrometry. Methanolic extracts, chemical, chromatographic fractions and spinasterol was evaluated against RAW 264.7, M12.C3.F6, PC-3, LS-180, A549 and HeLa cancer cell lines by the standardized method MTT for determinate the antiproliferative activity. Methanolic extract of stem shown the better antiproliferative activity against the murine macrophage cancer cell line RAW 264.7. n-Hexane chemical fraction shown antiproliferative activity against human alveolar cancer cell line A549 and RAW 264.7. Was isolated and characterized a compound by NMR 1H and 13C, revealing the presence of sterol spinasterol. Spinasterol shown to have antiproliferative activity against cervical cancer cell line HeLa and RAW 264.7, indicating that spinasterol can be a responsible compound of antiproliferative activity found in the methanolic extract of Stegnosperma halimifolium.

Antiproliferative activity of standardized herbal phytopreparation from Asclepias subulata.

Background: Several studies have shown that active compounds of Asclepias subulata (cardenolides) have antiproliferative effect on human cancer cells. Cardenolides isolated from A. subulata can be used as active chemical markers to elaborate phytopharmaceutical preparations. To evaluate the antiproliferative effect of a standardized extract of the aerial parts, based on Asclepias subulata cardenolides. Methods: Four standardized extracts were prepared by HPLC-DAD depending on the concentration of calotropin and the antiproliferative activity was measured for the MTT assay, on the A549, MCF-7, HeLa, PC3 and ARPE cell lines. The concentrations of calotropin used for the standardization of the extracts were 10, 7.6, 5 and 1 mg/dL. Results: Standardization of the A. subulata extract based on calotropin at 7.6 mg/g dry weight was achieved and the antiproliferative activity was evaluated over A549, HeLa and MCF-7 cell lines, obtaining proliferation percentages of 3.8 to 13.4% . Conclusions: The standardized extracts of A. subulata at different concentrations of calotropin showed antiproliferative activity against all the cell lines evaluated. The greatest effect was observed against the HeLa cell line.