5-IODOTUBERCIDIN

Chemical Properties

Tan Solid

Uses

A potent and competitive inhibitor of ERK2, PKA, and ADK.

Uses

5-Iodotubercidin has been used for the inhibition of retinoblastoma cells, astroglial cultures and for the inhibition of adenosine kinase in human umbilical vein endothelial cells (HUVECs).

Uses

An analogue of the antibiotic tubercidin, a pyrrolo[2,3-d]pyrimidine nucleoside antibiotic. A potent inhibitor of adenosine kinase from rat or guinea pig brain. Inhibits uptake of 3H-adenosine into brain slices.

General Description

solubility: 10 mg/mL in DMSO

Biological Activity

Potent adenosine kinase inhibitor (IC 50 = 26 nM) and nucleoside transporter inhibitor (IC 50 values are 7, 15 and < 25 nM for inhibition of [ 3 H]-uridine, [ 3 H]-formycin B and [ 3 H]-adenosine uptake respectively). Strongly stimulates glycogen synthesis in hepatocytes via activation of glycogen synthase. Also inhibits CK1, insulin receptor tyrosine kinase, phosphorylase kinase, PKA, CK2 and PKC (IC 50 values are 0.4, 3.5, 5-10, 5-10, 10.9 and 27.7 μ M respectively).

Biochem/physiol Actions

Potent inhibitor of adenosine uptake into brain, and of adenosine kinase and subsequent metabolism of adenine nucleotides. In cultured rat hepatocytes, 5-iodotubercidin inhibits both acetyl-CoA carboxylase and de novo synthesis of fatty acids and cholesterol.

Synthesis

A mixture of (2R,3R,4R,5R)-2-((benzoyloxy)methyl)-5-(4-chloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)tetrahydrofuroyl-3,4-diyl dibenzoate (3.0 g, 4.1 mmol) was used as a raw material, and a mixture of it with aqueous ammonia solution (45 ml) and 1,4-dioxane (45 ml) was reacted at 80 °C The reaction was stirred for 16 hours. The completion of the reaction was confirmed by LC-MS analysis. The reaction mixture was concentrated to remove the solvent to give a residue. The residue was suspended in a solvent mixture of CH2Cl2/MeOH (9:1) and purified by passing through a column pre-filled with silica gel (using CH2Cl2/MeOH (9:1→1:1) as eluent). The eluate containing the target product was collected and concentrated to afford (2R,3R,4S,5R)-2-(4-amino-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol (1.1 g, 69% yield) as a white solid. The product was characterized by 1H NMR (DMSO-d6): δ 8.10 (s, 1H), 7.68 (s, 1H), 6.68 (br s, 2H), 6.03 (d, 1H), 5.33 (br s, 1H), 5.15 (br, 2H), 4.36 (br s, 1H), 4.07 (br s, 1H), 3.88 (m, 1H). 3.56 (m, 2H).

storage

Store at -20°C

References

[1]. xin zhang, deyong jia, huijuan liu, et al. identification of 5-iodotubercidin as a genotoxic drug with anti-cancer potential. plos one, 2013, 8(5):e62527.
[2]. jaoek park and radhey s. gupta. adenosine: a key link between metabolism and brain activity: adenosine metabolism, adenosine kinase, and evolution. new york: springer science+business media, 2013.
[3]. garcía-villafranca j. and castro j. effects of 5-iodotubercidin on hepatic fatty acid metabolism mediated by the inhibition of acetyl-coa carboxylase. biochem. pharmacol., 2002, 63(11):1997-2000.
[4]. haiyan chen, ji-ping wang, richard j. santen, et al. adenosine monophosphate activated protein kinase (ampk), a mediator of estradiol-induced apoptosis in long-term estrogen deprived breast cancer cells. apoptosis, 2015, 20:821-830.