title: Evaluation of novel aryloxyalkyl derivatives of imidazole and 1,2,4-triazole as heme oxygenase-1 (HO-1) inhibitors and their antitumor properties.
abstract: A novel series of aryloxyalkyl derivatives of imidazole and 1,2,4-triazole, 17-31, 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. The most potent compounds 6 and 30 were selected and studied for their antitumor properties in a model of LAMA-84 R cell line overexpressing HO-1 and resistant to imatinib mesylate (IM), a tyrosine-kinase inhibitor used in the treatment of multiple types of cancer, most notably Philadelphia Chromosome positive (Ph(+)) Chronic Myelogenous Leukemia (CML). Results show that both 6 and 30 sensitized LAMA-84 R cell line to antitumor properties of IM.
authors.affiliation: Department of Drug Sciences, Section of Medicinal Chemistry, University of Catania, viale A. Doria 6, 95125 Catania, Italy. l.salerno@unict.it
authors.forename: Loredana
authors.initials: L
authors.lastname: Salerno
authors.forename: Valeria
authors.initials: V
authors.lastname: Pittalà
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Romeo
authors.forename: Maria N
authors.initials: MN
authors.lastname: Modica
authors.forename: Maria A
authors.initials: MA
authors.lastname: Siracusa
authors.forename: Claudia
authors.initials: C
authors.lastname: Di Giacomo
authors.forename: Rosaria
authors.initials: R
authors.lastname: Acquaviva
authors.forename: Ignazio
authors.initials: I
authors.lastname: Barbagallo
authors.forename: Daniele
authors.initials: D
authors.lastname: Tibullo
authors.forename: Valeria
authors.initials: V
authors.lastname: Sorrenti
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D001921:Brain / Q000201:enzymology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000201:enzymology; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D007093:Imidazoles; D012333:RNA, Messenger; D014230:Triazoles; C045575:1,2,4-triazole; C029899:imidazole; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C105245:heme oxygenase-2
keywords: 1,2,4-Triazole; Antitumor properties; HO-1inhibitors; Imatinib; Imidazole