Allopurinol riboside

Names

[ Name ]:
Allopurinol riboside

[Synonym ]:
8-Aza-6-hydroxy-7-deazapurine riboside
Allopurinol ribonucleoside
8-AZA-7-DEAZAINOSINE
<4-Hydroxy-1H-pyrazolo<3,4-d>pyrimidin>-ribosid
Allopurinol-1-ribonucleoside

Biological Activity

[Description]:

Allopurinol riboside, a metabolite of allopurinol, shows potent activities against parasites.

[Related Catalog]:

Signaling Pathways >> Anti-infection >> Parasite

Research Areas >> Infection

Natural Products >> Saccharides and Glycosides

[Target]

Human Endogenous Metabolite

[In Vitro]

Allopurinol-riboside competitively inhibits the action of purine nucleoside phosphorylase on inosine with a Ki of 277 μM. Lymphocyte blastogensis induced by PHA and Con A is significantly suppressed by allopurinol-riboside in a concentration-dependent manner. When LPS is used as a mitogen, the inhibition of allopurinol-ribosideon lymphocyte proliferation is less marked. Humoral immunity is not suppressed by allopurinol-riboside[1]. Allopurinol riboside is an experimental agent for the treatment of leishmaniasis and American trypanosomiasis. Allopurinol riboside is effective against parasites, because a series of enzymes (analogous to those that mediate purine salvage in humans) convert it into 4-aminopyrazolopyrimidine ribonucleoside triphosphate, a cytotoxic product. Allopurinol riboside is selectively toxic, because it is not metabolized by the corresponding enzymes in humans[2].

[In Vivo]

Allopurinol riboside peaks in plasma 1.6 hours after administration, has an elimination half-life of 3 hours, and steady-state concentrations in the therapeutic range[3]. After oral administration, unexpectedly low levels of allopurinol riboside in plasma are attributable to incomplete absorption and rapid renal clearance. Probenecid reduces the renal clearance of allopurinol riboside, extends the half-life of allopurinol riboside in plasma, and triples the levels of allopurinol riboside in plasma[4].

[References]

[1]. Nishida Y, et al. Inhibition of purine nucleoside phosphorylase activity and of T-cell function with allopurinol-riboside. Agents Actions. 1979 Dec;9(5-6):549-52.

[2]. Pacher P, et al. Therapeutic effects of xanthine oxidase inhibitors: renaissance half a century after the discovery of allopurinol. Pharmacol Rev. 2006 Mar;58(1):87-114.

[3]. Shapiro TA, et al. Pharmacokinetics and metabolism of allopurinol riboside. Clin Pharmacol Ther. 1991 May;49(5):506-14.

[4]. Were JB, et al. Effects of probenecid on the pharmacokinetics of allopurinol riboside. Antimicrob Agents Chemother. 1993 May;37(5):1193-6.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
2.08g/cm3

[ Boiling Point ]:
570.9ºC at 760mmHg

[ Molecular Formula ]:
C₁₀H₁₂N₄O₅

[ Molecular Weight ]:
268.22600

[ Flash Point ]:
299ºC

[ Exact Mass ]:
268.08100

[ PSA ]:
133.49000

[ Vapour Pressure ]:
3.62E-15mmHg at 25°C

[ Index of Refraction ]:
1.925

MSDS

Click to get detail MSDS

Safety Information

[ Personal Protective Equipment ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ RIDADR ]:
NONH for all modes of transport

[ WGK Germany ]:
3

Articles

Activity of inosine analogs against Pneumocystis carinii in culture.

Antimicrob. Agents Chemother. 30(1) , 181-3, (1986)

Three analogs of inosine, formycin B, allopurinol ribonucleoside, and 9-deazainosine, were tested for their ability to suppress proliferation of Pneumocystis carinii in culture with WI-38 cells. The o...

A tissue culture system for the growth of several species of Leishmania: growth kinetics and drug sensitivities.

Am. J. Trop. Med. Hyg. 38(2) , 304-7, (1988)

We have developed a simple in vitro method of infecting a continuous human macrophage cell line (U937) with promastigotes of several species of Leishmania. These include L. braziliensis braziliensis, ...

On the metabolism of allopurinol. Formation of allopurinol-1-riboside in purine nucleoside phosphorylase deficiency.

Biochem. Pharmacol. 32(14) , 2167-74, (1983)

Allopurinol-1-riboside, a major metabolite of allopurinol, is commonly thought to be directly synthesized by purine nucleoside phosphorylase (PNP) in vivo. As this enzyme is otherwise believed to func...