Synthesis and In Vitro Biological Evaluation of -Carborane-Based Di--butylphenol Analogs.

Targeting inflammatory mediators and related signaling pathways may offer a rational strategy for the treatment of cancer. The incorporation of metabolically stable, sterically demanding, and hydrophobic carboranes in dual cycloxygenase-2 (COX-2)/5-lipoxygenase (5-LO) inhibitors that are key enzymes in the biosynthesis of eicosanoids is a promising approach. The di--butylphenol derivatives , , , and represent potent dual COX-2/5-LO inhibitors. The incorporation of -carborane and further substitution of the -position resulted in four carborane-based di--butylphenol analogs that showed no or weak COX inhibition but high 5-LO inhibitory activities in vitro. Cell viability studies on five human cancer cell lines revealed that the -carborane analogs , , , and exhibited lower anticancer activity compared to the related di--butylphenols. Interestingly, did not affect the viability of primary cells and suppressed HCT116 cell proliferation more potently than its carbon-based counterpart. Considering all the advantages of boron cluster incorporation for enhancement of drug biostability, selectivity, and availability of drugs, can be tested in further mechanistic and in vivo studies.