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

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

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Keywords

Nitric oxide
Nitric oxide synthase
Tetrahydrobiopterin
Tetrahydroisoquinoline

ASJC Scopus subject areas

Pharmacology
Drug Discovery
Organic Chemistry

Cite this

Seo, J., Srisook, E., Son, H. J., Hwang, O., Cha, Y. N., & Chi, D. Y. (2008). Syntheses of tetrahydroisoquinoline derivatives that inhibit NO production in activated BV-2 microglial cells. European Journal of Medicinal Chemistry, 43(6), 1160-1170. https://doi.org/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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AU - Cha, Young Nam

AU - Chi, Dae Yoon

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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.

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KW - Tetrahydroisoquinoline

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10.1016/j.ejmech.2007.09.009