title: Second generation 2-aminoimidazole based advanced glycation end product inhibitors and breakers.
abstract: The formation of advanced glycation end-products (AGE) as a result of the action of reducing sugars on host macromolecules plays a role in increased morbidity of diabetic patients. There are currently no clinically available therapeutics for the prevention or eradication of AGEs. Following our previous identification of 2-aminoimidazole (2-AI) based AGE inhibitors and breakers, we now report the use of a rapid, scalable, two-step procedure to access a second generation of 2-AI based anti-AGE compounds from commercially available amino acids. Several second generation compounds exhibit increased AGE inhibition and breaking activty compared to the first generation compounds and to the known AGE inhibitor aminoguanidine.
authors.affiliation: Department of Chemistry, North Carolina State University, Raleigh, NC 27695, USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Furlani
authors.affiliation: Department of Microbiology, Immunology and Pathology, Mycobacteria Research Laboratories, Colorado State University, Fort Collins, CO 80524, USA.
authors.forename: Mike A
authors.initials: MA
authors.lastname: Richardson
authors.affiliation: Department of Microbiology, Immunology and Pathology, Mycobacteria Research Laboratories, Colorado State University, Fort Collins, CO 80524, USA.
authors.forename: Brendan K
authors.initials: BK
authors.lastname: Podell
authors.affiliation: Department of Microbiology, Immunology and Pathology, Mycobacteria Research Laboratories, Colorado State University, Fort Collins, CO 80524, USA.
authors.forename: David F
authors.initials: DF
authors.lastname: Ackart
authors.affiliation: Department of Microbiology, Immunology and Pathology, Mycobacteria Research Laboratories, Colorado State University, Fort Collins, CO 80524, USA.
authors.forename: Jessica D
authors.initials: JD
authors.lastname: Haugen
authors.affiliation: Department of Chemistry, North Carolina State University, Raleigh, NC 27695, USA.
authors.forename: Roberta J
authors.initials: RJ
authors.lastname: Melander
authors.affiliation: Department of Microbiology, Immunology and Pathology, Mycobacteria Research Laboratories, Colorado State University, Fort Collins, CO 80524, USA.
authors.forename: Randall J
authors.initials: RJ
authors.lastname: Basaraba
authors.affiliation: Department of Chemistry, North Carolina State University, Raleigh, NC 27695, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Melander
mesh_terms: D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D017127:Glycation End Products, Advanced; D007093:Imidazoles; C014973:2-aminoimidazole
keywords: 2-Aminoimidazole; Advanced glycation end-product (AGE); Akabori; Diabetes