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Bioorg Med Chem Lett. 2000 Jan 3;10(1):87-90.

Antioxidant function of phenethyl-5-bromo-pyridyl thiourea compounds with potent anti-HIV activity.

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Drug Discovery Program, Department of Chemistry, Hughes Institute, St Paul, MN 55113, USA.


In a systematic search for novel dual function antioxidants with potent anti-HIV activity, we evaluated 9 rationally designed non-nucleoside inhibitors (NNI) of HIV-1 RT for antioxidant and anti-HIV activities. Our lead phenethyl-5-bromopyridyl thiourea (PEPT) compounds, N-[2-(2-methoxyphenylethyl)]-N'-[2-(5-bromopyridyl)]-thioure a (2) and N-[2-(2-chlorophenylethyl)]-N'-[2-(5-bromopyridyl)]-thiourea (9), inhibited the oxidation of ABTS to ABTS*+ by metmyoglobin in the presence of hydrogen peroxide with EC50 values of 79 and 75 microM, respectively. Both compounds effectively inhibited the oxidation-induced green fluorescence emission from the free radical-sensitive indicator dye 2',7'-dichlorodihydrofluorescein diacetate in CEM human T-cells and Nalm-6 human B-cells exposed to hydrogen peroxide. To our knowledge, compounds 2 and 9 are the first NNI of HIV-1 RT with potent anti-oxidant activity. Furthermore, the activity center was defined as the sulfhydryl group since alkylated PEPT derivatives were inactive. The presence of a free thiourea group was also essential for the anti-HIV activity of the PEPT compounds.

[Indexed for MEDLINE]

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