Biochemical basis for a cholesterol-lowering activity of 2-[2'-(1',3'-dioxolane)]-2-methyl-4-(2'-oxo-1'-pyrrolidinyl)-6-nitro-2H-1 -benzopyran (SKP-450), a novel antihypertensive agent

Eun Young Lee, Dong Min Lim, Sung Eun Yoo, Dae Kee Kim, Young-Ki Paik

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Administration (p.o.) of SKP 450, 2-[2'-(1',3'-dioxolane)]-2-methyl-4-(2'-oxo-1'-pyrrolidinyl)-6-nitro-2H-1 -benzopyran, a novel antihypertensive agent, to hypercholesterolemic Syrian hamsters led to a significant reduction in plasma lipids in a dose-dependent manner, i.e., a 10.8% to 29% reduction in low-density lipoprotein cholesterol at doses of 0.3 to 10 mg/kg of SKP-450. SKP-450 was found to specifically inhibit the hepatic microsomal lanosterol 14α-methyl demethylase (14α-DM) in a competitive manner (K(i):2.65 μM). Furthermore, a dose dependent decrease in the 14α-DM activity by SKP 450 parallelled the cholesterol synthetic rate in vitro in both the rat hepatic S 10 fractions (supernatants at 10,000 g; IC 50 :20 μM) and Chinese hamster ovary cells (IC 50 :23 μM) However, this phenomenon was not seen in AR45 cells, which are deficient in 14α-DM, suggesting that 14α-DM is the major target for the inhibitory action of SKP-450 in regard to cholesterol biosynthesis.

Original languageEnglish
Pages (from-to)579-582
Number of pages4
JournalBiochemical Pharmacology
Volume57
Issue number5
DOIs
Publication statusPublished - 1999 Mar 1

Fingerprint

Benzopyrans
Antihypertensive Agents
Cholesterol
S 10
Lanosterol
Liver
Biosynthesis
Mesocricetus
Cricetulus
LDL Cholesterol
Rats
Ovary
Cells
KR 30450
2-methyldioxolane
Lipids
Plasmas

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology

Cite this

@article{05704a6bf3f442bfa563a8562d46ff96,
title = "Biochemical basis for a cholesterol-lowering activity of 2-[2'-(1',3'-dioxolane)]-2-methyl-4-(2'-oxo-1'-pyrrolidinyl)-6-nitro-2H-1 -benzopyran (SKP-450), a novel antihypertensive agent",
abstract = "Administration (p.o.) of SKP 450, 2-[2'-(1',3'-dioxolane)]-2-methyl-4-(2'-oxo-1'-pyrrolidinyl)-6-nitro-2H-1 -benzopyran, a novel antihypertensive agent, to hypercholesterolemic Syrian hamsters led to a significant reduction in plasma lipids in a dose-dependent manner, i.e., a 10.8{\%} to 29{\%} reduction in low-density lipoprotein cholesterol at doses of 0.3 to 10 mg/kg of SKP-450. SKP-450 was found to specifically inhibit the hepatic microsomal lanosterol 14α-methyl demethylase (14α-DM) in a competitive manner (K(i):2.65 μM). Furthermore, a dose dependent decrease in the 14α-DM activity by SKP 450 parallelled the cholesterol synthetic rate in vitro in both the rat hepatic S 10 fractions (supernatants at 10,000 g; IC 50 :20 μM) and Chinese hamster ovary cells (IC 50 :23 μM) However, this phenomenon was not seen in AR45 cells, which are deficient in 14α-DM, suggesting that 14α-DM is the major target for the inhibitory action of SKP-450 in regard to cholesterol biosynthesis.",
author = "Lee, {Eun Young} and Lim, {Dong Min} and Yoo, {Sung Eun} and Kim, {Dae Kee} and Young-Ki Paik",
year = "1999",
month = "3",
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volume = "57",
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}

Biochemical basis for a cholesterol-lowering activity of 2-[2'-(1',3'-dioxolane)]-2-methyl-4-(2'-oxo-1'-pyrrolidinyl)-6-nitro-2H-1 -benzopyran (SKP-450), a novel antihypertensive agent. / Lee, Eun Young; Lim, Dong Min; Yoo, Sung Eun; Kim, Dae Kee; Paik, Young-Ki.

In: Biochemical Pharmacology, Vol. 57, No. 5, 01.03.1999, p. 579-582.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Biochemical basis for a cholesterol-lowering activity of 2-[2'-(1',3'-dioxolane)]-2-methyl-4-(2'-oxo-1'-pyrrolidinyl)-6-nitro-2H-1 -benzopyran (SKP-450), a novel antihypertensive agent

AU - Lee, Eun Young

AU - Lim, Dong Min

AU - Yoo, Sung Eun

AU - Kim, Dae Kee

AU - Paik, Young-Ki

PY - 1999/3/1

Y1 - 1999/3/1

N2 - Administration (p.o.) of SKP 450, 2-[2'-(1',3'-dioxolane)]-2-methyl-4-(2'-oxo-1'-pyrrolidinyl)-6-nitro-2H-1 -benzopyran, a novel antihypertensive agent, to hypercholesterolemic Syrian hamsters led to a significant reduction in plasma lipids in a dose-dependent manner, i.e., a 10.8% to 29% reduction in low-density lipoprotein cholesterol at doses of 0.3 to 10 mg/kg of SKP-450. SKP-450 was found to specifically inhibit the hepatic microsomal lanosterol 14α-methyl demethylase (14α-DM) in a competitive manner (K(i):2.65 μM). Furthermore, a dose dependent decrease in the 14α-DM activity by SKP 450 parallelled the cholesterol synthetic rate in vitro in both the rat hepatic S 10 fractions (supernatants at 10,000 g; IC 50 :20 μM) and Chinese hamster ovary cells (IC 50 :23 μM) However, this phenomenon was not seen in AR45 cells, which are deficient in 14α-DM, suggesting that 14α-DM is the major target for the inhibitory action of SKP-450 in regard to cholesterol biosynthesis.

AB - Administration (p.o.) of SKP 450, 2-[2'-(1',3'-dioxolane)]-2-methyl-4-(2'-oxo-1'-pyrrolidinyl)-6-nitro-2H-1 -benzopyran, a novel antihypertensive agent, to hypercholesterolemic Syrian hamsters led to a significant reduction in plasma lipids in a dose-dependent manner, i.e., a 10.8% to 29% reduction in low-density lipoprotein cholesterol at doses of 0.3 to 10 mg/kg of SKP-450. SKP-450 was found to specifically inhibit the hepatic microsomal lanosterol 14α-methyl demethylase (14α-DM) in a competitive manner (K(i):2.65 μM). Furthermore, a dose dependent decrease in the 14α-DM activity by SKP 450 parallelled the cholesterol synthetic rate in vitro in both the rat hepatic S 10 fractions (supernatants at 10,000 g; IC 50 :20 μM) and Chinese hamster ovary cells (IC 50 :23 μM) However, this phenomenon was not seen in AR45 cells, which are deficient in 14α-DM, suggesting that 14α-DM is the major target for the inhibitory action of SKP-450 in regard to cholesterol biosynthesis.

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