title: Fused imidazoles as potential chemical scaffolds for inhibition of heat shock protein 70 and induction of apoptosis. Synthesis and biological evaluation of phenanthro[9,10-d]imidazoles and imidazo[4,5-f][1,10]phenanthrolines.
abstract: The imidazole ring is widespread in biologically active compounds, and hence imidazole-containing scaffolds are useful starting points for drug discovery programmes. We report the synthesis of a series of novel imidazole-containing compounds fused with either phenanthrene or phenanthroline, which show enhanced growth inhibitory potency against human colon, breast and melanoma cancer cell lines, as well as evidence of inhibition of the molecular chaperone heat shock protein 70 (Hsp70) pathway in cells, as shown by depletion of downstream oncogenic client proteins of the Hsp90 chaperone pathway, and induction of apoptosis.
authors.affiliation: School of Chemistry, University of Nottingham, University Park, Nottingham, NG7 2RD, UK. c.j.moody@nottingham.ac.uk.
authors.forename: Alpa
authors.initials: A
authors.lastname: Patel
authors.forename: Swee Y
authors.initials: SY
authors.lastname: Sharp
authors.forename: Katelan
authors.initials: K
authors.lastname: Hall
authors.forename: William
authors.initials: W
authors.lastname: Lewis
authors.forename: Malcolm F G
authors.initials: MF
authors.lastname: Stevens
authors.forename: Paul
authors.initials: P
authors.lastname: Workman
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Moody
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D018840:HSP70 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D007093:Imidazoles / Q000737:chemistry* / Q000494:pharmacology*; D010618:Phenanthrolines / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D018840:HSP70 Heat-Shock Proteins; D007093:Imidazoles; D010618:Phenanthrolines