Design, synthesis and activity of benzothiazole-based inhibitors of NO production in LPS-activated macrophages.
Series of benzothiazoles were synthesized and evaluated their inhibitory activities for NO production in lipopolysaccharide-activated macrophages. The most potent compound was the indole-containing benzothiazole 3c with 4.18μM of IC(50). The mechanistic study suggested that benzothiazoles inhibited NO production by the suppression of iNOS protein and mRNA expression. They also suppressed the expression of COX-2 through the NF-κB inactivation.
Jin
Guo Hua
GH
College of Pharmacy, Sookmyung Women's University, 52 Hyochangwon-Gil, Yongsan-Ku, Seoul 140-742, Republic of Korea.
Li
Hua
H
An
Semi
S
Ryu
Jae-Ha
JH
Jeon
Raok
R
D000818:Animals; D052160:Benzothiazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D013058:Mass Spectrometry; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013329:Structure-Activity Relationship; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000378:metabolism
D052160:Benzothiazoles; D052246:Cyclooxygenase 2 Inhibitors; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II