Synthesis of phenylisothiourea derivatives as inhibitors of NO production in LPS activated macrophages.
A series of phenylisothioureas were synthesized as inhibitors of NO production in lipopolysaccharide-activated macrophages. We investigated the effect of lipophilic moiety and N- or S-substituents of the phenylisothioureas on the activity. Inhibitory activities of carbazole-linked phenylisothioureas were superior to the corresponding simple phenylisothiourea derivatives. Among these compounds, 12b having N-ethyl and S-isopropyl groups on phenylisothiourea moiety was the most potent in the inhibition of NO production. They inhibited NO production through the suppression of the LPS-induced translocation of p65 subunit of NF-kappaB and the followed suppression of the iNOS protein and mRNA expression.
Jin
Guo Hua
GH
College of Pharmacy, Sookmyung Women's University, Seoul, Republic of Korea. kinne@ihi-zittau.de
Lee
Da Yeon
DY
Cheon
Ye-Jin
YJ
Gim
Hyo Jin
HJ
Kim
Do Hee
do H
Kim
Hee-Doo
HD
Ryu
Jae-Ha
JH
Jeon
Raok
R
D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D013890:Thiourea / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D008070:Lipopolysaccharides; D016328:NF-kappa B; D009569:Nitric Oxide; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D013890:Thiourea