Abstract
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 μM 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 BH 4-dependent dimerization of the newly synthesized iNOS monomer.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3369-3373 |
| Number of pages | 5 |
| Journal | Bioorganic and Medicinal Chemistry Letters |
| Volume | 15 |
| Issue number | 14 |
| DOIs | |
| State | Published - Jul 15 2005 |
| Externally published | Yes |
Fingerprint
Keywords
- Inhibition of NO
- Inhibition of tetrahydrobiopterin
- NAMDA
- Nitric oxide
- Nitric oxide synthase
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry
Cite this
Syntheses of NAMDA derivatives inhibiting NO production in BV-2 cells stimulated with lipopolysaccharide. / Seo, Jai; Srisook, Ekaruth; Hyo, Jin Son; Hwang, Onyou; Cha, Young Nam; Dae, Yoon Chi.
In: Bioorganic and Medicinal Chemistry Letters, Vol. 15, No. 14, 15.07.2005, p. 3369-3373.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Syntheses of NAMDA derivatives inhibiting NO production in BV-2 cells stimulated with lipopolysaccharide
AU - Seo, Jai
AU - Srisook, Ekaruth
AU - Hyo, Jin Son
AU - Hwang, Onyou
AU - Cha, Young Nam
AU - Dae, Yoon Chi
PY - 2005/7/15
Y1 - 2005/7/15
N2 - 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 μM 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 BH 4-dependent dimerization of the newly synthesized iNOS monomer.
AB - 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 μM 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 BH 4-dependent dimerization of the newly synthesized iNOS monomer.
KW - Inhibition of NO
KW - Inhibition of tetrahydrobiopterin
KW - NAMDA
KW - Nitric oxide
KW - Nitric oxide synthase
UR - http://www.scopus.com/inward/record.url?scp=20644437763&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=20644437763&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2005.05.033
DO - 10.1016/j.bmcl.2005.05.033
M3 - Article
C2 - 15953725
AN - SCOPUS:20644437763
VL - 15
SP - 3369
EP - 3373
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 14
ER -