title: A substituted 3,4-dihydropyrimidinone derivative (compound D22) prevents inflammation mediated neurotoxicity; role in microglial activation in BV-2 cells.
abstract: A novel synthetic 3,4-dihydropyrimidinone derivative, compound D22 (ethyl 6-methyl-4-(3-phenoxyphenyl)-2-thioxo-3,4-dihydropyrimidine-5-carboxylate), was found to exert anti-inflammatory properties in lipopolysaccharide-stimulated microglial BV-2 cells. Compound D22 reduced the pro-inflammatory factors such as nitric oxide, prostaglandin E(2), tumor necrosis factor-α and interleukin-1β. Moreover, it suppressed the expressions of inducible NO synthase and cyclooxygenase-2. Compound D22 inhibited the activation of mitogen-activated protein kinases. When compound D22-conditioned media from BV-2 cells were applied to N2a cells, neuronal cell death was inhibited via suppression of caspase-3 activation and regulation of Bcl-2 and Bax proteins expression. These results suggest that compound D22 may be useful for treating neurodegenerative diseases related with neuroinflammation.
authors: Graduate School of East-West Medical Science, Kyung Hee University Global Campus, #1732 Deogyeong-daero, Giheung-gu, Yongin, Gyeonggi-do 446-701, Republic of Korea.
authors: Oh Wook
authors: OW
authors: Kwon
authors: Eunjung
authors: E
authors: Moon
authors: Murugulla A
authors: MA
authors: Chari
authors: Tae Woo
authors: TW
authors: Kim
authors: Ae-jung
authors: AJ
authors: Kim
authors: Pyeongjae
authors: P
authors: Lee
authors: Kwang-Hyun
authors: KH
authors: Ahn
authors: Sun Yeou
authors: SY
authors: Kim
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013871:Thiones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D018675:Toxicity Tests; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D019253:Proto-Oncogene Proteins c-bcl-2; D011743:Pyrimidines; D013871:Thiones; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; C576472:ethyl 6-methyl-4-(3-phenoxyphenyl)-2-thioxo-3,4-dihydropyrimidine-5-carboxylate; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases; D053148:Caspase 3; D015232:Dinoprostone