Novel dual cyclooxygenase and lipoxygenase inhibitors targeting hyaluronan-CD44v6 pathway and inducing cytotoxicity in colon cancer cells

The structural analogs of 2,6 di-tert-butyl-p-benzoquinone (BQ) appended with hydrazide side chain were found to inhibit COX-2 and 5-LOX at micromolar concentrations. Molecular docking of the compounds into COX-2 and 5-LOX protein cavities indicated strong binding interactions supporting the observed cytotoxicities. It has been observed for the first time, that three of our COX/5-LOX dual inhibitors inhibit proliferation upon hydrazide substitution preventing the activity of pro-angiogenic factors in HCA-7, HT-29, Apc10.1 cells as well as prohibit the hyaluronan synthase-2 (Has2) enzyme over-expressed in colon cancer cells, through inhibition of the hyaluronan/CD44v6 cell survival pathway.