title: Systematic mining of generally recognized as safe (GRAS) flavor chemicals for bioactive compounds.
abstract: Bioactive food compounds can be both therapeutically and nutritionally relevant. Screening strategies are widely employed to identify bioactive compounds from edible plants. Flavor additives contained in the so-called FEMA GRAS (generally recognized as safe) list of approved flavoring ingredients is an additional source of potentially bioactive compounds. This work used the principles of molecular similarity to identify compounds with potential mood-modulating properties. The ability of certain GRAS molecules to inhibit histone deacetylase-1 (HDAC1), proposed as an important player in mood modulation, was assayed. Two GRAS chemicals were identified as HDAC1 inhibitors in the micromolar range, results similar to what was observed for the structurally related mood prescription drug valproic acid. Additional studies on bioavailability, toxicity at higher concentrations, and off-target effects are warranted. The methodology described in this work could be employed to identify potentially bioactive flavor chemicals present in the FEMA GRAS list.
authors.affiliation: Instituto de Química, UNAM , Avenida Universidad 3000, Mexico City 04510, Mexico.
authors.forename: Karina
authors.initials: K
authors.lastname: Martinez-Mayorga
authors.forename: Terry L
authors.initials: TL
authors.lastname: Peppard
authors.forename: Fabian
authors.initials: F
authors.lastname: López-Vallejo
authors.forename: Austin B
authors.initials: AB
authors.lastname: Yongye
authors.forename: José L
authors.initials: JL
authors.lastname: Medina-Franco
mesh_terms: D000928:Antidepressive Agents / Q000737:chemistry; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000737:chemistry; D005421:Flavoring Agents / Q000737:chemistry*; D056284:Histone Deacetylase 1 / Q000037:antagonists & inhibitors; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry*; D010945:Plants, Edible / Q000737:chemistry*
chemical_list: D000928:Antidepressive Agents; D004791:Enzyme Inhibitors; D005421:Flavoring Agents; D010936:Plant Extracts; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1