Study of metabolism of the antiviral drug arbidol by mass spectrometry, thin-layer and high-performance liquid chromatography

Анисимова, О. С.; Frolova, L. V.; Chistyakov, V. V.; Ermachenkov, I. A.; Golovanova, I. V.; Zotova, S. A.; Плешкова, А. П.; Yadrovskaya, V. A.; Sheinker, Yu. N.

doi:10.1007/bf02226513

Cited by 6 publications

(4 citation statements)

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“…1A): oxidation at the sulfur atom, loss of the 4-(dimethylamino)methyle group and N-demethylation, conjugation at the 5-hydroxyl moiety. In a pioneering study in rat urine, the formation of sulfone and sulfoxide forms was confirmed after HPLC, from an oral administration of an ARB/starch suspension (Anisimova et al, 1995). Glucuronide or sulfate conjugations were also observed at position 5, and after demethylation of the (dimethylamino)methyle group (see also Liu et al, 2012).…”

Section: Arb Bioavailability Pharmacokinetics and Metabolismmentioning

confidence: 92%

Arbidol as a broad-spectrum antiviral: An update

2014

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Arbidol (ARB) is a Russian-made small indole-derivative molecule, licensed in Russia and China for prophylaxis and treatment of influenza and other respiratory viral infections. It also demonstrates inhibitory activity against other viruses, enveloped or not, responsible for emerging or globally prevalent infectious diseases such as hepatitis B and C, gastroenteritis, hemorrhagic fevers or encephalitis. In this review, we will explore the possibility and pertinence of ARB as a broad-spectrum antiviral, after a careful examination of its physico-chemical properties, pharmacokinetics, toxicity, and molecular mechanisms of action. Recent studies suggest that ARB's dual interactions with membranes and aromatic amino acids in proteins may be central to its broad-spectrum antiviral activity. This could impact on the virus itself, and/or on cellular functions or critical steps in virus-cell interactions, thereby positioning ARB as both a direct-acting antiviral (DAA) and a host-targeting agent (HTA). In the context of recent studies in animals and humans, we will discuss the prospective clinical use of ARB in various viral infections.

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Section: Arb Bioavailability Pharmacokinetics and Metabolismmentioning

confidence: 92%

Arbidol as a broad-spectrum antiviral: An update

2014

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“…Indeed, in the urine of mice fed with ARB, up to 12 ARB metabolites have been detected, of which some were oxidized sulfoxide and sulfone forms of ARB. Using thin-layer chromatography, HPLC and mass spectrometry, ARB metabolites were identified and quantified in chloroform extracts of urine of rats fed with ARB [14]. It was revealed that three metabolites exceeded the content of the unchanged ARB compound.…”

Section: Arb Pharmacokineticsmentioning

confidence: 99%

Arbidol: A Broad-Spectrum Antiviral Compound that Blocks Viral Fusion

Boriskin

Ленева²,

Pécheur³

et al. 2008

CMC

371

316

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Arbidol (ARB; ethyl-6-bromo-4-[(dimethylamino)methyl]-5-hydroxy-1-methyl-2-[(phenylthio)methyl]-indole-3-carboxylate hydrochloride monohydrate), is a Russian-made potent broad-spectrum antiviral with demonstrated activity against a number of enveloped and non-enveloped viruses. ARB is well known in Russia and China, although to a lesser extent in western countries. Unlike other broad-spectrum antivirals, ARB has an established molecular mechanism of action against influenza A and B viruses, which is different from that of available influenza antivirals, and a more recently established mechanism of inhibition of hepatitis C virus (HCV). For both viral infections the anti-viral mechanism involves ARB inhibition of virus-mediated fusion with target membrane and a resulting block of virus entry into target cells. However, ARB inhibition of fusion exploits different ARB modalities in case of influenza viruses or HCV. This review aims to summarize the available evidence of ARB effects against different groups of viruses, also, to compare various aspects of ARB anti-fusion mechanisms against influenza virus and HCV (with reference to different stringency of pH-dependence of these two viral fusogens) and to discuss further prospects for ARB and its improved derivatives of the parent compounds.

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“…Arbidol is an antiviral active chemical entity created by the Chemical Drug Center of All Russian Research Institute of Pharmaceutical Chemistry together with the Institute of Medical Radiology 1. Early reports showed that arbidol inhibits influenza virus–induced membrane fusion and may have the capacity to induce serum interferon 2, 3.…”

Section: Introductionmentioning

confidence: 99%

“…Literature search resulted in a single article published in 1995 1. The metabolites of arbidol from rat urine were identified by the use of thin‐layer chromatography (TLC/LC) coupled with mass spectrometry 1. No human metabolic study of arbidol has been reported so far.…”

Section: Introductionmentioning

confidence: 99%

Metabolite identification of arbidol in human urine by the study of CID fragmentation pathways using HPLC coupled with ion trap mass spectrometry

Wang

Chen

et al. 2008

J. Mass Spectrom.

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The metabolism of arbidol in humans was studied using liquid chromatography-electrospray ionization (ESI) ion trap mass spectrometry (ITMS) after an oral dose of 300-mg arbidol. A total of 17 metabolites were identified including the glucuronide arbidol and the glucuronide sulfinylarbidol as the major metabolites. Arbidol and its metabolites have some common fragmentation patterns as a result of a homolytic bond cleavage. This cleavage will form odd-electron ions with the loss of a radical. The arbidol fragmentation sequence is first to lose dimethylamine (45 Da), followed by the loss of acetaldehyde (44 Da), and then the phenylthio radical (109 Da). This fragmentation sequence is also observed from N-demethylarbidol, sulfonylarbidol, and N-demethylsulfonylarbidol. However, for sulfinylarbidol and N-demethylsulfinylarbidol, the fragmentation sequence is reversed so that the phenylsulfiny radical (125 Da) was lost first, followed by the loss of dimethylamine (45 Da), and then acetaldehyde (44 Da). The exact masses for arbidol and sulfinylarbidol fragment ions were determined by a quadrupole/time-of-flight mass spectrometer (Q-TOF MS). The phase II metabolites, such as sulfate and glucuronide conjugates of arbidol, N-demethylarbidol, sulfonylarbidol, and N-demethylsulfonylarbidol were identified by observing the neutral loss of 80 Da (SO(3)) or 176 Da (glucuronic acid) from the MS(2) spectra. The sulfate and glucuronide conjugates such as sulfinylarbidol and N-demethylsulfinylarbidol had an unusual fragmentation pattern, in which the phenylsulfinyl radical (125 Da) was lost before the loss of SO(3) group (80 Da) or glucuronic acid (176 Da) occurred.

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Study of metabolism of the antiviral drug arbidol by mass spectrometry, thin-layer and high-performance liquid chromatography

Cited by 6 publications

References 0 publications

Arbidol as a broad-spectrum antiviral: An update

Arbidol as a broad-spectrum antiviral: An update

Arbidol: A Broad-Spectrum Antiviral Compound that Blocks Viral Fusion

Metabolite identification of arbidol in human urine by the study of CID fragmentation pathways using HPLC coupled with ion trap mass spectrometry

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