Differential Effect of Wortmannolone Derivatives on MDA-MB-231 Breast Cancer Cells.

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).

Curley, Robert W,JrOhio State University, USA (författare)
Fatima, NighatQuaid-i-Azam University, Pakistan;University of Hawaii at Hilo, USA (författare)
Ahmed, SafiaQuaid-i-Azam University, Pakistan (författare)
Chang, Leng CheeUniversity of Hawaii at Hilo, USA (författare)
De Blanco, Esperanza J CarcacheOhio State University, USA (författare)
Ohio State University, USAQuaid-i-Azam University, Pakistan;University of Hawaii at Hilo, USA (creator_code:org_t)

Ingår i:Anticancer Research: International Institute of Anticancer Research37:4, s. 1617-16230250-70051791-7530

Av författaren/redakt...: Acuña, Ulyana Mu ...; Curley, Robert W ...; Fatima, Nighat; Ahmed, Safia; Chang, Leng Chee; De Blanco, Esper ...

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