Anti-neuroinflammatory activity of 1,5-benzodiazepine derivatives.
A series of 2,3-dihydro-1,5-benzodiazepines were synthesized and evaluated for anti-inflammatory effects in microglia cells. Among the 1,5-benzodiazepines tested, compound 3e strongly inhibited LPS-induced nitric oxide (NO) production, with an IC(50) value of 7.0microM in the microglia cells. Also, compound 3e significantly inhibited the enzymatic activity of inducible NO synthase (iNOS) without changes in iNOS protein expression or NO scavenging activity. This result suggests that compound 3e showed anti-neuroinflammatory effects by suppressing iNOS enzyme activity.
Ha
Sang Keun
SK
Kyung Hee University, Giheung-gu, Yongin, Gyeonggi-do, Republic of Korea.
Shobha
Donthabhaktuni
D
Moon
Eunjung
E
Chari
Murugulla A
MA
Mukkanti
Kagga
K
Kim
Sung-Hoon
SH
Ahn
Kwang-Hyun
KH
Kim
Sun Yeou
SY
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001569:Benzodiazepines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D015394:Molecular Structure; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; D013876:Thiophenes; D001569:Benzodiazepines; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II