title: Synthesis and biological evaluation in human monocyte-derived macrophages of N-(N-acetyl-L-cysteinyl)-S-acetylcysteamine analogues with potent antioxidant and anti-HIV activities.
abstract: We synthesized a series of N-(N-acetyl-L-cysteinyl)-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 > or = 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.
authors.affiliation: Laboratoire de Chimie Organique Biomoléculaire de Synthèse, UMR CNRS-UM II 5625, Université Montpellier II Sciences et Techniques du Languedoc, place Eugène Bataillon, 34095 Montpellier, France. clayette@dsvidf.cea.fr
authors.forename: Joël
authors.initials: J
authors.lastname: Oiry
authors.forename: Patricia
authors.initials: P
authors.lastname: Mialocq
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Puy
authors.forename: Philippe
authors.initials: P
authors.lastname: Fretier
authors.forename: Nathalie
authors.initials: N
authors.lastname: Dereuddre-Bosquet
authors.forename: Dominique
authors.initials: D
authors.lastname: Dormont
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Imbach
authors.forename: Pascal
authors.initials: P
authors.lastname: Clayette
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000975:Antioxidants / Q000138:chemical synthesis* / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008264:Macrophages / Q000187:drug effects* / Q000821:virology; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D000975:Antioxidants; D005978:Glutathione; D000111:Acetylcysteine