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) |
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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 |
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