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  • Acuña, Ulyana Muñoz, et al. (författare)
  • Differential Effect of Wortmannolone Derivatives on MDA-MB-231 Breast Cancer Cells.
  • 2017
  • Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 37:4, s. 1617-1623
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND/AIM: The survival rate of women diagnosed with triple-negative breast-cancer (TNBC) remains low. Hence, this study aimed at the chemical and biological optimization of furanosteroid derivatives for the treatment of this type of malignancy using TNBC cells.MATERIALS AND METHODS: Semi-synthetic analogs of wortmannolone (1-6) that negatively affected the aberrant pathways in tumor cells were evaluated in hormone-independent breast cancer cells using western blot and cell-cycle analysis.RESULTS: Wortmannolone derivatization generated NF-ĸB inhibitors as new lead structures for further development. Compound (3) was found to be the most significantly active lead.CONCLUSION: Structure-activity analysis in the present study showed that acetylation of the hydroxyl groups and substitution on C3 and C17 of wortmannolone enhanced biological activity. Alpha-substitution of the acetyl group in C3 on ring A (compound 3) resulted in ROS inducing effect; however, presence of an acetyl group in β-position of C3 displayed the highest NF-ĸB p65 inhibitory activity (0.60 μM).
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