title: Design, synthesis, and biological evaluation of hydroquinone derivatives as novel inhibitors of the sarco/endoplasmic reticulum calcium ATPase.
abstract: Analogues of the compound 2,5-di-tert-butylhydroquinone (BHQ) are capable of inhibiting the enzyme sarco/endoplasmic reticulum ATPase (SERCA) in the low micromolar and submicromolar concentration ranges. Not only are SERCA inhibitors valuable research tools, but they also have potential medicinal value as agents against prostate cancer. This study describes the synthesis of 13 compounds representing several classes of BHQ analogues, such as hydroquinones with a single aromatic substituent, symmetrically and unsymmetrically disubstituted hydroquinones, and hydroquinones with omega-amino acid tethers attached to their hydroxyl groups. Structure-activity relationships were established by measuring the inhibitory potencies of all synthesized compounds in bioassays. The assays were complemented by computational ligand docking for an analysis of the relevant ligand/receptor interactions.
authors.affiliation: Department of Chemistry, Natural Sciences Center, Northern Kentucky University, Highland Heights, KY 41099-1905, United States. paulas1@nku.edu
authors.forename: Stefan
authors.initials: S
authors.lastname: Paula
authors.forename: Josh
authors.initials: J
authors.lastname: Abell
authors.forename: Joel
authors.initials: J
authors.lastname: Deye
authors.forename: Christopher
authors.initials: C
authors.lastname: Elam
authors.forename: Michael
authors.initials: M
authors.lastname: Lape
authors.forename: Justin
authors.initials: J
authors.lastname: Purnell
authors.forename: Robert
authors.initials: R
authors.lastname: Ratliff
authors.forename: Kelly
authors.initials: K
authors.lastname: Sebastian
authors.forename: Jodie
authors.initials: J
authors.lastname: Zultowsky
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Kempton
mesh_terms: D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D003198:Computer Simulation; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D006873:Hydroquinones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D013329:Structure-Activity Relationship
chemical_list: D006873:Hydroquinones; D000252:Calcium-Transporting ATPases
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