Novel lipoic acid analogues that inhibit nitric oxide synthase.
The synthesis and biological activity of novel lipoic acid analogues are reported. Lipoic acid and structural homologues coupled to arylthiophene amidine via carboxamide linkers are metabolic antioxidants capable of protecting neuronal cells against glutamate cytotoxicity, preventing loss of intracellular glutathione, and inhibit nitric oxide synthase.
Harnett
Jeremiah J
JJ
Department of Medicinal Chemistry, Beaufour-Ipsen Research Laboratories, Institute Henri Beaufour, 5, Avenue du Canada, 91966 Cedex, Les Ulis, France. jeremiah.harnett@beaufour-ipsen.com
Auguet
Michel
M
Viossat
Isabelle
I
Dolo
Christine
C
Bigg
Dennis
D
Chabrier
Pierre-E
PE
D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis / Q000494:pharmacology; D001120:Arginine / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002956:Citrulline / Q000378:metabolism; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism / Q000633:toxicity; D005978:Glutathione / Q000172:deficiency / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000138:chemical synthesis / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000633:toxicity; D052248:Nitric Oxide Synthase Type I; D018384:Oxidative Stress / Q000187:drug effects; D008063:Thioctic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
D000975:Antioxidants; D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D002956:Citrulline; D018698:Glutamic Acid; D008063:Thioctic Acid; D001120:Arginine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; D005978:Glutathione