Novel di-tertiary-butyl phenylhydrazones as dual cyclooxygenase-2/5-lipoxygenase inhibitors: Synthesis, COX/LOX inhibition, molecular modeling, and insights into their cytotoxicities

The novel structural analogs 3,5 di-tert-butyl hydrazones represent a potent class of compounds inhibiting the COX/LOX pro-inflammatory cytokines efficiently at lower micromolar concentrations. Our results show that the novel COX-LOX inhibitors inhibit the proliferation of a panel of human colon cancer cell lines including HCA-7, HT-29, SW480 and Apc10.1 cells as well as the hyaluronan synthase-2 (Has2) enzyme over-expressed in colon cancer cells, through inhibition of the hyaluronan/CD44v6 cell survival pathway.