A new cytotoxic sesquiterpene lactone from Euphorbia microsphaera Boiss against human breast cancer (MCF-7) and human fibrosarcoma (HT1080) cells.

A new guaianolide sesquiterpene lactone with cytotoxic properties was isolated from Euphorbia microsphaera Boiss. To determine the highest active fraction and isolate bioactive compounds, a bioassay guided fractionation approach was used. The general toxicity properties of the plant's extracts and fractions (fr) were assessed against Artemia salina, Oryzeaphilus mercator, and Tribolium castaneum. Cytotoxic activities were investigated against normal human foreskin fibroblasts and two malignant cell lines, including human breast cancer (MCF-7) and human fibrosarcoma cells (HT1080) using the MTT assay at different time points of 24, 48, and 72 h. Single crystal X-ray diffraction (SC-XRD) and mass spectrometry data were used to determine the structure of the active guaianolide sesquiterpene lactone (3aR,4S,4aS,5R,7aS,9aS)-5-hydroxy-5,8-dimethyl-3-methylene-2-oxo-2,3,3a,4,4a,5,6,7,7a, 9a decahydroazuleno [6,5-b] furan-4-yl acetate (named aryanin). Chloroformic fraction 7 (fr, LC = 93.50 μg/mL for general toxicity) had the highest toxicity result, with a mortality rate of more than 50% for both insect species after 12 h at 15 mg/mL. The highest cytotoxicity of aryanin was observed on 24 h treated MCF-7 with an IC of 13.81 μg/mL. After 24 h, the inhibition of MCF-7 cell proliferation was 92%-94% at concentrations of 25-50 μg/mL, respectively. On MCF-7, the IC was found to be 49.35 μg/mL after 72 h. This compound had a considerable cytotoxicity (IC ≤ 12.5 μg/mL, 24 h) on human foreskin fibroblasts. In contrast to the MCF-7 cell line, the proliferation of human foreskin fibroblasts was increased after 72 h.