Syntheses of NAMDA derivatives inhibiting NO production in BV-2 cells stimulated with lipopolysaccharide.
Sixteen derivatives of N-acetyl-3-O-methyldopamine (NAMDA), an inhibitor of BH4 synthesis, were designed and synthesized. The ability of these derivatives to inhibit NO and BH4 production by lipopolysaccharide-stimulated BV-2 microglial cells was determined. While NAMDA at 100 microM inhibited NO and BH4 production by only about 20%, its catecholamide 8, indole 23 derivative, 13, and N-acetyl tetrahydroisoquinoline 25 inhibited the NO production by >50% at the same concentration. In particular, 13 and 25 inhibited both NO and BH4 production to similar degrees, which suggested that these compounds might inhibit NO production by blocking BH4-dependent dimerization of the newly synthesized iNOS monomer.
Seo
Jai Woong
JW
Department of Chemistry, Inha University, 253 Yonghyundong Namgu, Inchon 402-751, Republic of Korea.
Srisook
Ekaruth
E
Son
Hyo Jin
HJ
Hwang
Onyou
O
Cha
Young-Nam
YN
Chi
Dae Yoon
DY
D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004298:Dopamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D015394:Molecular Structure; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D013329:Structure-Activity Relationship
D008070:Lipopolysaccharides; C117276:N-acetyl-3-O-methyldopamine; D001708:Biopterins; D009569:Nitric Oxide; D007770:L-Lactate Dehydrogenase; C003402:sapropterin; D004298:Dopamine