PMID- 26446934
OWN - NLM
STAT- MEDLINE
DCOM- 20170324
LR  - 20171116
IS  - 1475-6374 (Electronic)
IS  - 1475-6366 (Linking)
VI  - 31
IP  - 5
DP  - 2016 Oct
TI  - New synthetic AICAR derivatives with enhanced AMPK and ACC activation.
PG  - 748-53
LID - 10.3109/14756366.2015.1063622 [doi]
AB  - 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 
      alpha (AMPKalpha), 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.
FAU - Scudiero, Olga
AU  - Scudiero O
AD  - a CEINGE - Advanced Biotechnologies S.C a r.l. , Napoli , Italy .
AD  - b Department of Molecular Medicine and Medical Biotechnologies and.
FAU - Nigro, Ersilia
AU  - Nigro E
AD  - a CEINGE - Advanced Biotechnologies S.C a r.l. , Napoli , Italy .
FAU - Monaco, Maria Ludovica
AU  - Monaco ML
AD  - a CEINGE - Advanced Biotechnologies S.C a r.l. , Napoli , Italy .
FAU - Oliviero, Giorgia
AU  - Oliviero G
AD  - c Department of Pharmacy , University of Naples Federico II , Napoli , Italy .
FAU - Polito, Rita
AU  - Polito R
AD  - a CEINGE - Advanced Biotechnologies S.C a r.l. , Napoli , Italy .
FAU - Borbone, Nicola
AU  - Borbone N
AD  - c Department of Pharmacy , University of Naples Federico II , Napoli , Italy .
FAU - D'Errico, Stefano
AU  - D'Errico S
AD  - c Department of Pharmacy , University of Naples Federico II , Napoli , Italy .
FAU - Mayol, Luciano
AU  - Mayol L
AD  - c Department of Pharmacy , University of Naples Federico II , Napoli , Italy .
FAU - Daniele, Aurora
AU  - Daniele A
AD  - a CEINGE - Advanced Biotechnologies S.C a r.l. , Napoli , Italy .
AD  - d Department of Environmental Biological and Pharmaceutical Sciences and 
      Technologies , Second University of Naples , Caserta , Italy , and.
FAU - Piccialli, Gennaro
AU  - Piccialli G
AD  - c Department of Pharmacy , University of Naples Federico II , Napoli , Italy .
AD  - e Institute of Protein Biochemistry , Napoli , Italy.
LA  - eng
PT  - Journal Article
DEP - 20151008
PL  - England
TA  - J Enzyme Inhib Med Chem
JT  - Journal of enzyme inhibition and medicinal chemistry
JID - 101150203
RN  - 0 (Ribonucleotides)
RN  - 360-97-4 (Aminoimidazole Carboxamide)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - EC 6.4.1.2 (Acetyl-CoA Carboxylase)
RN  - F0X88YW0YK (AICA ribonucleotide)
SB  - IM
MH  - AMP-Activated Protein Kinases/genetics/*metabolism
MH  - Acetyl-CoA Carboxylase/genetics/*metabolism
MH  - Aminoimidazole Carboxamide/*analogs & derivatives/chemical 
      synthesis/chemistry/pharmacology
MH  - Blotting, Western
MH  - Cell Line, Tumor
MH  - Enzyme Activation/drug effects
MH  - Gene Expression Regulation, Enzymologic/*drug effects
MH  - Humans
MH  - MAP Kinase Signaling System/genetics
MH  - Molecular Structure
MH  - Ribonucleotides/*chemical synthesis/chemistry/*pharmacology
OTO - NOTNLM
OT  - ACC
OT  - AICAR
OT  - AMPK
OT  - cell lines cytotoxicity
OT  - p-ERK1/2
EDAT- 2015/10/09 06:00
MHDA- 2017/03/25 06:00
CRDT- 2015/10/09 06:00
PHST- 2015/10/09 06:00 [entrez]
PHST- 2015/10/09 06:00 [pubmed]
PHST- 2017/03/25 06:00 [medline]
AID - 10.3109/14756366.2015.1063622 [doi]
PST - ppublish
SO  - J Enzyme Inhib Med Chem. 2016 Oct;31(5):748-53. doi: 
      10.3109/14756366.2015.1063622. Epub 2015 Oct 8.