Evaluation of novel aryloxyalkyl derivatives of imidazole and 1,2,4-triazole as Heme Oxygenase-1 inhibitors and their antitumor properties

A novel series of aryloxyalkyl derivatives of imidazole and 1,2,4-triazole was designed and synthesized as inhibitors of heme oxygenase-1 (HO-1) and heme oxygenase-2 (HO-2). Some of these compounds were found to be good inhibitors of HO-1, in particular those carrying an imidazole moiety as azolyl group and a 3-bromo or 4-iodophenyl as aryl moiety. Most potent compounds, 1-[4-(3-bromophenoxy)butyl]-1H-imidazole and 1-[4-(4-iodophenoxy)butyl]-1H-imidazole, were selected and studied for their antitumor properties in a model of LAMA-84 R cell line overexpressing HO-1 and resistant to imatinib (IM) mesylate, a tyrosine-kinase inhibitor used in the treatment of multiple cancers, most notably of which includes Philadelphia Chromosome positive (Ph+) Chronic Myelogenous Leukemia (CML). Results show that both compounds sensitized LAMA-84 R cell line to antitumor properties of IM.