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Abstract

Various mechanisms for regulated cell death include the formation of oxidative mediators such as lipid peroxides and nitric oxide (NO). In this respect, 15-lipoxygenase-1 (15-LOX-1) is a key enzyme that catalyzes the formation of lipid peroxides. The actions of these peroxides are interconnected with nuclear factor-?B signaling and NO production. Inhibition of 15-LOX-1 holds promise to interfere with regulated cell death in inflammatory conditions. In this study, a novel potent 15-LOX-1 inhibitor, 9c (i472), was developed and structure-activity relationships were explored. In vitro, this inhibitor protected cells from lipopolysaccharide-induced cell death, inhibiting NO formation and lipid peroxidation. Thus, we provide a novel 15-LOX-1 inhibitor that inhibits cellular NO production and lipid peroxidation, which set the stage for further exploration of these mechanisms.

Original languageEnglish
Pages (from-to)4624-4637
Number of pages14
JournalJournal of Medicinal Chemistry
Volume62
Issue number9
Early online date9-Apr-2019
DOIs
Publication statusPublished - 9-May-2019

Keywords

  • SELECTIVE INHIBITORS
  • NITRIC-OXIDE
  • IN-VITRO
  • POTENT
  • ACID
  • ACTIVATION
  • IDENTIFICATION
  • LIPOXYGENASE
  • DERIVATIVES
  • MECHANISMS

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