title: A broadly neuroprotective derivative of curcumin.
abstract: The plant polyphenolic curcumin alters the response of nerve cells to some forms of toxic stress. The steroid-like compound, cyclohexyl bisphenol A, has broad neuroprotective properties that are very distinct from those of curcumin. To incorporate both families of biological activities into a single molecule, a pyrazole derivative of curcumin, called CNB-001, was synthesized. CNB-001 acquires a new activity and is far superior in neuroprotection assays to either parental molecule, but retains some of the properties of both. It is neuroprotective in cell culture assays for trophic factor withdrawal, oxidative stress, excitotoxicity, and glucose starvation, as well as toxicity from both intracellular and extracellular amyloid. While the creation of CNB-001 was based upon an uncommon approach to drug design, it has the potential of a lead drug candidate for treating multiple conditions involving nerve cell death.
authors.affiliation: The Salk Institute, Laboratories for Cellular Neurobiology, La Jolla, California 92037-1099, USA.
authors.forename: Yuanbin
authors.initials: Y
authors.lastname: Liu
authors.forename: Richard
authors.initials: R
authors.lastname: Dargusch
authors.forename: Pamela
authors.initials: P
authors.lastname: Maher
authors.forename: David
authors.initials: D
authors.lastname: Schubert
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003474:Curcumin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D051379:Mice; D018696:Neuroprotective Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011720:Pyrazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats
chemical_list: C529348:CNB 001; D018696:Neuroprotective Agents; D011720:Pyrazoles; D003474:Curcumin