title: New synthetic AICAR derivatives with enhanced AMPK and ACC activation.
abstract: 5-Aminoimidazole-4-carboxamide riboside (AICAR) has an important role in the regulation of the cellular metabolism showing a broad spectrum of therapeutic activities against different metabolic processes. Due to these proven AICAR properties, we have designed, synthesized and tested the biological activity of two ribose-modified AICAR derivatives, named A3 and A4, in comparison to native AICAR and its 5'-phosphorylated counterpart ZMP. Our findings have shown that A3 and A4 derivatives induce the phosphorylation of 5'-AMP activated protein kinase α (AMPKα), which leads to the inhibition of acetyl-CoA carboxylase (ACC), and down-regulate the activity of the extracellular signal-regulated kinases (ERK1/2). Cytotoxicity tests demonstrated that A3 and A4 do not significantly reduce cell viability up to 24 h. Taken together our results indicate that A3 and A4 have a comparable activity to AICAR and ZMP at 0.5 and 1 mM suggesting their potential use in future pharmacological strategies relating to metabolic diseases.
authors.affiliation: a CEINGE - Advanced Biotechnologies S.C a r.l. , Napoli , Italy .|b Department of Molecular Medicine and Medical Biotechnologies and.
authors.forename: Olga
authors.initials: O
authors.lastname: Scudiero
authors.affiliation: a CEINGE - Advanced Biotechnologies S.C a r.l. , Napoli , Italy .
authors.forename: Ersilia
authors.initials: E
authors.lastname: Nigro
authors.affiliation: a CEINGE - Advanced Biotechnologies S.C a r.l. , Napoli , Italy .
authors.forename: Maria Ludovica
authors.initials: ML
authors.lastname: Monaco
authors.affiliation: c Department of Pharmacy , University of Naples Federico II , Napoli , Italy .
authors.forename: Giorgia
authors.initials: G
authors.lastname: Oliviero
authors.affiliation: a CEINGE - Advanced Biotechnologies S.C a r.l. , Napoli , Italy .
authors.forename: Rita
authors.initials: R
authors.lastname: Polito
authors.affiliation: c Department of Pharmacy , University of Naples Federico II , Napoli , Italy .
authors.forename: Nicola
authors.initials: N
authors.lastname: Borbone
authors.affiliation: c Department of Pharmacy , University of Naples Federico II , Napoli , Italy .
authors.forename: Stefano
authors.initials: S
authors.lastname: D'Errico
authors.affiliation: c Department of Pharmacy , University of Naples Federico II , Napoli , Italy .
authors.forename: Luciano
authors.initials: L
authors.lastname: Mayol
authors.affiliation: a CEINGE - Advanced Biotechnologies S.C a r.l. , Napoli , Italy .|d Department of Environmental Biological and Pharmaceutical Sciences and Technologies , Second University of Naples , Caserta , Italy , and.
authors.forename: Aurora
authors.initials: A
authors.lastname: Daniele
authors.affiliation: c Department of Pharmacy , University of Naples Federico II , Napoli , Italy .|e Institute of Protein Biochemistry , Napoli , Italy.
authors.forename: Gennaro
authors.initials: G
authors.lastname: Piccialli
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000103:Acetyl-CoA Carboxylase / Q000235:genetics / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D015394:Molecular Structure; D012265:Ribonucleotides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase; C031143:AICA ribonucleotide
keywords: ACC; AICAR; AMPK; cell lines cytotoxicity; p-ERK1/2