Design and synthesis of urea and thiourea derivatives and their inhibitory activities on lipopolysaccharide-induced NO production.
Series of ureas and thioureas were designed and synthesized, and their inhibitory activities of NO production in lipopolysaccharide-activated macrophages were evaluated. We found several essential moieties in the structure of the prepared compounds for the activity. Thiourea derivatives revealed higher inhibitory activity than the corresponding urea derivatives. Among these compounds, 7e having carboxymethyl group at N3 position of thiourea was the most potent in the inhibition of NO production. They inhibited NO production through the suppression of iNOS protein and mRNA expression.
Kim
Yoon Jung
YJ
College of Pharmacy, Sookmyung Women's University, 52 Hyochangwon-Gil, Yongsan-Ku, Seoul 140-742, Republic of Korea.
Ryu
Jae-Ha
JH
Cheon
Ye Jin
YJ
Lim
Hyo Jin
HJ
Jeon
Raok
R
D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors*; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008956:Models, Chemical; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013329:Structure-Activity Relationship; D013890:Thiourea / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology*; D014508:Urea / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology*
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D009569:Nitric Oxide; D014508:Urea; D052247:Nitric Oxide Synthase Type II; D013890:Thiourea