Synthesis and biological evaluation in human monocyte-derived macrophages of N-(N-acetyl-L-cysteinyl)-S-acetyleysteamine analogues with potent antioxidant and anti-HTV activities

We synthesized a series of N-(N-acetyl-L-eysteinyl)-S-acetylcysteamine (10) analogues bearing various acyl groups on thiol cysteine or cysteamine residues, to investigate the structure-activity relationship for pro-GSH and anti-HIV properties in human macrophages. The S-substituents were ranked in t...

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Published inJournal of medicinal chemistry Vol. 47; no. 7; pp. 1789 - 1795
Main Authors Oiry, J, Mialocq, P, Puy, JY, Fretier, P, Dereuddre-Bosquet, N, Dormont, D, Imbach, JL, Clayette, P
Format Journal Article
LanguageEnglish
Published WASHINGTON Amer Chemical Soc 25.03.2004
Subjects
Chemistry, Medicinal
Life Sciences & Biomedicine
Pharmacology & Pharmacy
Science & Technology
INDIVIDUALS
OXIDATIVE STRESS
HIV-INFECTION
REPLICATION
GLUTATHIONE DEFICIENCY
INFLAMMATION
ALPHA SYNTHESIS INHIBITOR
N-ACETYLCYSTEINE
HUMAN-IMMUNODEFICIENCY-VIRUS
EXPRESSION
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Summary:We synthesized a series of N-(N-acetyl-L-eysteinyl)-S-acetylcysteamine (10) analogues bearing various acyl groups on thiol cysteine or cysteamine residues, to investigate the structure-activity relationship for pro-GSH and anti-HIV properties in human macrophages. The S-substituents were ranked in the following order of efficacy: H greater than or equal to acetyl > isobutyryl > pivaloyl > benzoyl. We found that none of these derivatives had pro-GSH or antiviral activities in vitro higher than that of 10, but several displayed similar levels of anti-HIV activity, making them possible candidates for use as adjuvant therapies in conjunction with HAART, for treating neurological aspects of HIV infection.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm030374d