We recently reported a series of N-cyclopropylbenzamide-benzophenone hybrid molecules as novel and selective p38 mitogen-activated protein kinase (MAPK) inhibitors. Among of them, NJK14047 showed excellent p38 MAPK inhibitory activity and selectivity. To investigate the therapeutic usefulness of NJK14047, we evaluated its anti-inflammatory activity, especially in the aspect of neuroinflammation. P38 MAPK has been identified as an essential enzyme with inflammatory roles in several immune cells, and its regulation is important to be potential therapeutic agents for neurodegenerative diseases. In this study, we showed that NJK14047 attenuates lipopolysaccharide (LPS)-stimulated neuroinflammation in BV2 microglia cells and an LPS-injected mice model. NJK14047 reduced the production of prostaglandin E2 and nitric oxide by downregulation of the expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), nitric oxide synthase (NOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated BV2 microglia. Moreover, in vivo model studies showed that NJK14047 significantly reduced microglial activation in the brains of LPS-injected mice.

Synthesis of N-cyclopropylbenzamide-benzophenone hybrids as novel and selective p38 mitogen-activated protein kinase inhibitors and their biological evaluation for neuroinflammation

2019 Fall National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.