In:
Advanced Therapeutics, Wiley, Vol. 6, No. 4 ( 2023-04)
Abstract:
The selective inhibition of enzymes that catalyze the conversion of arachidonic acid to inflammatory eicosanoids represents a promising approach for cancer therapy. This study, therefore, focuses on the incorporation of metabolically stable, sterically demanding, and hydrophobic carboranes into existing dual cycloxygenase‐2 (COX‐2)/5‐lipoxygenase (5‐LO) inhibitors that are key enzymes in the biosynthesis of eicosanoids. Here, the first carborane‐containing dual COX‐2/5‐LO inhibitors derived from RWJ‐63556 are presented. The replacement of the fluorophenyl moiety by meta ‐ or para ‐carborane resulted in five carborane‐containing derivatives 3 , 6 , 9 , 13 , and 17 that show high inhibitory activities toward COX‐2 and 5‐LO in vitro. Cell viability studies on the A375 melanoma cell line revealed that meta ‐carborane derivative 3 shows higher anticancer activity compared to RWJ‐63556 based on accumulation of lipid droplets in the cells due to blockage of the COX‐2 and 5‐LO pathways, indicating a promising approach for the design of potent dual COX‐2/5‐LO inhibitors.
Type of Medium:
Online Resource
ISSN:
2366-3987
,
2366-3987
DOI:
10.1002/adtp.202200252
Language:
English
Publisher:
Wiley
Publication Date:
2023
detail.hit.zdb_id:
2920320-X
