title: Structure-activity relationships of melanocortin agonists containing the benzimidazole scaffold.
abstract: The melanocortin system has been implicated in regulating various physiological processes including pigmentation, energy homeostasis, obesity, steroidogenesis cardiovascular, and exocrine gland function. The five melanocortin receptors that belong to the super family of G protein-coupled receptors are stimulated by naturally occurring agonists. The aim of this research was focused on the design, synthesis, and pharmacological characterization of melanocortin ligands that contain the 1,2,5-trisubstituted benzimidazole scaffold. A series of benzimidazole analogues, with three points of diversity at positions 1, 2, and 5, were designed, synthesized, pharmacologically assayed at the mouse melanocortin receptors MC1R, MC3R, MC4R, and MC5R and resulted in ligands possessing a range of agonist activity from nm to no stimulation at up to 100 microM concentrations. This study demonstrates that the benzimidazole structure template can be appended with key melanocortin agonist amino acids for the design melanocortin receptor agonist ligands.
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Todorovic
authors.forename: Christine G
authors.initials: CG
authors.lastname: Joseph
authors.forename: Nicholas B
authors.initials: NB
authors.lastname: Sorensen
authors.forename: Michael S
authors.initials: MS
authors.lastname: Wood
authors.forename: Carrie
authors.initials: C
authors.lastname: Haskell-Luevano
mesh_terms: D001562:Benzimidazoles / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D006801:Humans; D053486:Melanocortins / Q000819:agonists*; D013329:Structure-Activity Relationship
chemical_list: D001562:Benzimidazoles; D053486:Melanocortins