Synthesis of analogues of Congo red and evaluation of their anti-prion activity

Shane Sellarajah; Tamuna Lekishvili; Claire  Bowring; Andrew R. Thompsett; Helene Rudyk; Christopher R. Birkett; David R. Brown; Ian H. Gilbert

doi:10.1021/jm049922t

Synthesis of analogues of Congo red and evaluation of their anti-prion activity

Shane Sellarajah, Tamuna Lekishvili, Claire Bowring, Andrew R. Thompsett, Helene Rudyk, Christopher R. Birkett, David R. Brown, Ian H. Gilbert

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Abstract

No cure as of yet exists for any of the transmissible spongiform encephalopathies. In this paper, we describe the synthesis of analogues of Congo red and evaluation against a cellular model of infection, the SMB (scrapie mouse brain) persistently infected cell line, for their ability to inhibit the infectivity of the abnormal form of prion protein (PrP-res). The compounds have also been tested for their ability to inhibit the polymerization of PrPC by PrP-res. A number of analogues showed inhibition of PrP-res infectivity at nanomolar concentrations. Several analogues show promise; the most active compound, 2a, inhibits the formation of PrP-res in SMB cells with an EC50 of 25-50 nM.

Original language	English
Pages (from-to)	5515-5534
Number of pages	20
Journal	Journal of Medicinal Chemistry
Volume	47
Issue number	22
DOIs	https://doi.org/10.1021/jm049922t
Publication status	Published - 2004

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title = "Synthesis of analogues of Congo red and evaluation of their anti-prion activity",

abstract = "No cure as of yet exists for any of the transmissible spongiform encephalopathies. In this paper, we describe the synthesis of analogues of Congo red and evaluation against a cellular model of infection, the SMB (scrapie mouse brain) persistently infected cell line, for their ability to inhibit the infectivity of the abnormal form of prion protein (PrP-res). The compounds have also been tested for their ability to inhibit the polymerization of PrPC by PrP-res. A number of analogues showed inhibition of PrP-res infectivity at nanomolar concentrations. Several analogues show promise; the most active compound, 2a, inhibits the formation of PrP-res in SMB cells with an EC50 of 25-50 nM.",

author = "Shane Sellarajah and Tamuna Lekishvili and Claire Bowring and Thompsett, {Andrew R.} and Helene Rudyk and Birkett, {Christopher R.} and Brown, {David R.} and Gilbert, {Ian H.}",

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AU - Sellarajah, Shane

AU - Lekishvili, Tamuna

AU - Bowring, Claire

AU - Thompsett, Andrew R.

AU - Rudyk, Helene

AU - Birkett, Christopher R.

AU - Brown, David R.

AU - Gilbert, Ian H.

PY - 2004

Y1 - 2004

N2 - No cure as of yet exists for any of the transmissible spongiform encephalopathies. In this paper, we describe the synthesis of analogues of Congo red and evaluation against a cellular model of infection, the SMB (scrapie mouse brain) persistently infected cell line, for their ability to inhibit the infectivity of the abnormal form of prion protein (PrP-res). The compounds have also been tested for their ability to inhibit the polymerization of PrPC by PrP-res. A number of analogues showed inhibition of PrP-res infectivity at nanomolar concentrations. Several analogues show promise; the most active compound, 2a, inhibits the formation of PrP-res in SMB cells with an EC50 of 25-50 nM.

AB - No cure as of yet exists for any of the transmissible spongiform encephalopathies. In this paper, we describe the synthesis of analogues of Congo red and evaluation against a cellular model of infection, the SMB (scrapie mouse brain) persistently infected cell line, for their ability to inhibit the infectivity of the abnormal form of prion protein (PrP-res). The compounds have also been tested for their ability to inhibit the polymerization of PrPC by PrP-res. A number of analogues showed inhibition of PrP-res infectivity at nanomolar concentrations. Several analogues show promise; the most active compound, 2a, inhibits the formation of PrP-res in SMB cells with an EC50 of 25-50 nM.

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DO - 10.1021/jm049922t

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SP - 5515

EP - 5534

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 22

ER -

Synthesis of analogues of Congo red and evaluation of their anti-prion activity

Abstract

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