Syntheses of tetrahydroisoquinoline derivatives that inhibit NO production in activated BV-2 microglial cells

Jai Seo; Ekaruth Srisook; Hyo Jin Son; Onyou Hwang; Young Nam Cha; Dae Yoon Chi

doi:10.1016/j.ejmech.2007.09.009

Syntheses of tetrahydroisoquinoline derivatives that inhibit NO production in activated BV-2 microglial cells

Jai Seo, Ekaruth Srisook, Hyo Jin Son, Onyou Hwang, Young Nam Cha, Dae Yoon Chi

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

Abstract

Seventeen tetrahydroisoquinoline derivatives were designed, synthesized and evaluated for inhibition of NO production in lipopolysaccharide-stimulated BV-2 microglial cells. Compounds 5a, 9c and 11a potently attenuated NO production by >60%, and 5a and 11a inhibited BH4 production by >48% at 100 μM. In particular, N-ethylcarbonyl-7-hydroxy-6-methoxy-1,2,3,4-tetrahydroisoquinoline (11a) reduced NO production by 64% and tetrahydrobiopterin (BH4) production by 49%. Introducing longer alkyl component at C1 or N2 position led to attenuation of the inhibitory effect. It is possible that 11a inhibits NO production by blocking BH4-dependent dimerization of newly synthesized iNOS monomers.

Original language	English (US)
Pages (from-to)	1160-1170
Number of pages	11
Journal	European Journal of Medicinal Chemistry
Volume	43
Issue number	6
DOIs	https://doi.org/10.1016/j.ejmech.2007.09.009
State	Published - Jun 1 2008
Externally published	Yes

Keywords

Nitric oxide
Nitric oxide synthase
Tetrahydrobiopterin
Tetrahydroisoquinoline

ASJC Scopus subject areas

Pharmacology
Drug Discovery
Organic Chemistry

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10.1016/j.ejmech.2007.09.009

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title = "Syntheses of tetrahydroisoquinoline derivatives that inhibit NO production in activated BV-2 microglial cells",

abstract = "Seventeen tetrahydroisoquinoline derivatives were designed, synthesized and evaluated for inhibition of NO production in lipopolysaccharide-stimulated BV-2 microglial cells. Compounds 5a, 9c and 11a potently attenuated NO production by >60%, and 5a and 11a inhibited BH4 production by >48% at 100 μM. In particular, N-ethylcarbonyl-7-hydroxy-6-methoxy-1,2,3,4-tetrahydroisoquinoline (11a) reduced NO production by 64% and tetrahydrobiopterin (BH4) production by 49%. Introducing longer alkyl component at C1 or N2 position led to attenuation of the inhibitory effect. It is possible that 11a inhibits NO production by blocking BH4-dependent dimerization of newly synthesized iNOS monomers.",

keywords = "Nitric oxide, Nitric oxide synthase, Tetrahydrobiopterin, Tetrahydroisoquinoline",

author = "Jai Seo and Ekaruth Srisook and Son, {Hyo Jin} and Onyou Hwang and Cha, {Young Nam} and Chi, {Dae Yoon}",

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doi = "10.1016/j.ejmech.2007.09.009",

language = "English (US)",

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AU - Seo, Jai

AU - Srisook, Ekaruth

AU - Son, Hyo Jin

AU - Hwang, Onyou

AU - Cha, Young Nam

AU - Chi, Dae Yoon

PY - 2008/6/1

Y1 - 2008/6/1

N2 - Seventeen tetrahydroisoquinoline derivatives were designed, synthesized and evaluated for inhibition of NO production in lipopolysaccharide-stimulated BV-2 microglial cells. Compounds 5a, 9c and 11a potently attenuated NO production by >60%, and 5a and 11a inhibited BH4 production by >48% at 100 μM. In particular, N-ethylcarbonyl-7-hydroxy-6-methoxy-1,2,3,4-tetrahydroisoquinoline (11a) reduced NO production by 64% and tetrahydrobiopterin (BH4) production by 49%. Introducing longer alkyl component at C1 or N2 position led to attenuation of the inhibitory effect. It is possible that 11a inhibits NO production by blocking BH4-dependent dimerization of newly synthesized iNOS monomers.

AB - Seventeen tetrahydroisoquinoline derivatives were designed, synthesized and evaluated for inhibition of NO production in lipopolysaccharide-stimulated BV-2 microglial cells. Compounds 5a, 9c and 11a potently attenuated NO production by >60%, and 5a and 11a inhibited BH4 production by >48% at 100 μM. In particular, N-ethylcarbonyl-7-hydroxy-6-methoxy-1,2,3,4-tetrahydroisoquinoline (11a) reduced NO production by 64% and tetrahydrobiopterin (BH4) production by 49%. Introducing longer alkyl component at C1 or N2 position led to attenuation of the inhibitory effect. It is possible that 11a inhibits NO production by blocking BH4-dependent dimerization of newly synthesized iNOS monomers.

KW - Nitric oxide

KW - Nitric oxide synthase

KW - Tetrahydrobiopterin

KW - Tetrahydroisoquinoline

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Syntheses of tetrahydroisoquinoline derivatives that inhibit NO production in activated BV-2 microglial cells

Abstract

Keywords

ASJC Scopus subject areas

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