Synthesis of new N-isobutyryl-L-cysteine/MEA conjugates: evaluation of their free radical-scavenging activities and anti-HIV properties in human macrophages.
Four novel N-isobutyryl-L-cysteine/2-mercaptoethylamine (MEA, cysteamine) conjugates have been designed and synthesized. The antioxidant activities of these new series were evaluated by three different free radical scavenging methods (DPPH test, ABTS test, and deoxyribose assay) and their metal binding capacity was evaluated by the ethidium bromide fluorescence binding assay. These results were compared with those obtained with their pro-GSH acetyl analogues recently developed in our laboratory. We observed that most of these compounds exhibit free radical-scavenging activities similar to those of Trolox, but always superior than NAC. While none of these new derivatives had pro-GSH activities, they displayed anti-HIV properties in human monocyte-derived macrophages infected in vitro. The present study demonstrates that these new N-isobutyryl derivatives, which are expected to have a greater bioavailability than their acetyl analogues, may have useful applications in HIV infection in respect to their antioxidant and anti-HIV activities.
Smietana
Michael
M
Institut des Biomolécules Max Mousseron, IBMM UMR 5247 CNRS, Université Montpellier 1, Université Montpellier 2, place Eugène Bataillon, 34095 Montpellier, France. msmietana@univ-montp2.fr
Clayette
Pascal
P
Mialocq
Patricia
P
Vasseur
Jean-Jacques
JJ
Oiry
Joël
J
D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000975:Antioxidants / Q000737:chemistry; D003543:Cysteamine / Q000031:analogs & derivatives / Q000627:therapeutic use; D003545:Cysteine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016166:Free Radical Scavengers / Q000737:chemistry*; D006801:Humans; D008264:Macrophages / Q000821:virology*; D013329:Structure-Activity Relationship
D019380:Anti-HIV Agents; D000975:Antioxidants; D016166:Free Radical Scavengers; D003543:Cysteamine; D003545:Cysteine