Relaxant Effects of Flavonoids in Isolated Guinea Pig Trachea and Their Structure-Activity Relationships

Wun-Chang Ko, Pi Ying Liu, Junn Lain Chen, I. Jung Leu, Chwen Ming Shih

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The structure-activity relationships between flavonoids and their tracheal relaxant action are little known. In the present study, 26 natural and synthetic flavonoids, divided into the five classes of flavones, flavonols, flavanones, isoflavones, and chalcones, were tested, and their IC50 values were determined. The IC50 values of these five classes indicated that flavones were more potent than flavonols. Flavones were also more potent than flavanones suggesting that the presence of a double bond between C-2 and C-3 is important. However, flavones were similar to isoflavones in potency. Chalcones, a class with an open C-ring, appeared to be the least potent among these five classes. Introduction of a hydroxy group at position C-6 of flavones increases their relaxant activities. So does adding a hydroxy group at position C-7 of flavones. It appears that the optimal number of hydroxy groups introduced to the A-ring of flavones is one. As more hydroxy groups are introduced to positions at C-5, C-6, and/or C-7 of flavones, the IC50 values increase. It seems that flavones or flavonols with a pyrogallol moiety either in the A- or B-ring, respectively, have no activity. It appears that flavonols with ortho-hydroxy groups in the B-ring are more potent than those with meta-hydroxy groups. The activity of 6-hydroxyflavone disappears if the C-6 hydroxy group of the A-ring is methoxylated. If the C-4′ hydroxy group of the B ring is methoxylated, the relaxant effect of these flavones is also attenuated or disappears. Therefore, the hydroxy group on either the A- or B-ring of flavones and flavonols being methylated resulted in lower potency of the tracheal relaxant effects. However, when all hydroxy groups on both the A- and B-rings of flavones or flavonols are methoxylated this results in higher potency. Therefore, the influence of methoxylation in flavones may be similar to that in flavonols. However, if the C-3 hydroxy group on the C-ring of flavonols, but not flavones which lack this hydroxy group, is methoxylated, the relaxant effects may increase. Glycosylation of the hydroxy group at position C-7 of flavones or flavanones attenuates the relaxant effects.

Original languageEnglish
Pages (from-to)1086-1090
Number of pages5
JournalPlanta Medica
Volume69
Issue number12
DOIs
Publication statusPublished - Dec 2003

Fingerprint

Flavones
trachea (vertebrates)
structure-activity relationships
flavones
Structure-Activity Relationship
Trachea
Flavonoids
guinea pigs
Guinea Pigs
flavonoids
Flavonols
flavonols
Flavanones
flavanones
Chalcones
chalcones
Inhibitory Concentration 50
inhibitory concentration 50
Isoflavones
isoflavones

Keywords

  • Flavones
  • Flavonoids
  • Flavonols
  • Guinea pig
  • Isoflavone
  • Structure-activity relationships
  • Tracheal relaxant

ASJC Scopus subject areas

  • Plant Science
  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

Cite this

Relaxant Effects of Flavonoids in Isolated Guinea Pig Trachea and Their Structure-Activity Relationships. / Ko, Wun-Chang; Liu, Pi Ying; Chen, Junn Lain; Leu, I. Jung; Shih, Chwen Ming.

In: Planta Medica, Vol. 69, No. 12, 12.2003, p. 1086-1090.

Research output: Contribution to journalArticle

Ko, Wun-Chang ; Liu, Pi Ying ; Chen, Junn Lain ; Leu, I. Jung ; Shih, Chwen Ming. / Relaxant Effects of Flavonoids in Isolated Guinea Pig Trachea and Their Structure-Activity Relationships. In: Planta Medica. 2003 ; Vol. 69, No. 12. pp. 1086-1090.
@article{485795de7017490aba47cc021b472484,
title = "Relaxant Effects of Flavonoids in Isolated Guinea Pig Trachea and Their Structure-Activity Relationships",
abstract = "The structure-activity relationships between flavonoids and their tracheal relaxant action are little known. In the present study, 26 natural and synthetic flavonoids, divided into the five classes of flavones, flavonols, flavanones, isoflavones, and chalcones, were tested, and their IC50 values were determined. The IC50 values of these five classes indicated that flavones were more potent than flavonols. Flavones were also more potent than flavanones suggesting that the presence of a double bond between C-2 and C-3 is important. However, flavones were similar to isoflavones in potency. Chalcones, a class with an open C-ring, appeared to be the least potent among these five classes. Introduction of a hydroxy group at position C-6 of flavones increases their relaxant activities. So does adding a hydroxy group at position C-7 of flavones. It appears that the optimal number of hydroxy groups introduced to the A-ring of flavones is one. As more hydroxy groups are introduced to positions at C-5, C-6, and/or C-7 of flavones, the IC50 values increase. It seems that flavones or flavonols with a pyrogallol moiety either in the A- or B-ring, respectively, have no activity. It appears that flavonols with ortho-hydroxy groups in the B-ring are more potent than those with meta-hydroxy groups. The activity of 6-hydroxyflavone disappears if the C-6 hydroxy group of the A-ring is methoxylated. If the C-4′ hydroxy group of the B ring is methoxylated, the relaxant effect of these flavones is also attenuated or disappears. Therefore, the hydroxy group on either the A- or B-ring of flavones and flavonols being methylated resulted in lower potency of the tracheal relaxant effects. However, when all hydroxy groups on both the A- and B-rings of flavones or flavonols are methoxylated this results in higher potency. Therefore, the influence of methoxylation in flavones may be similar to that in flavonols. However, if the C-3 hydroxy group on the C-ring of flavonols, but not flavones which lack this hydroxy group, is methoxylated, the relaxant effects may increase. Glycosylation of the hydroxy group at position C-7 of flavones or flavanones attenuates the relaxant effects.",
keywords = "Flavones, Flavonoids, Flavonols, Guinea pig, Isoflavone, Structure-activity relationships, Tracheal relaxant",
author = "Wun-Chang Ko and Liu, {Pi Ying} and Chen, {Junn Lain} and Leu, {I. Jung} and Shih, {Chwen Ming}",
year = "2003",
month = "12",
doi = "10.1055/s-2003-45187",
language = "English",
volume = "69",
pages = "1086--1090",
journal = "Planta Medica",
issn = "0032-0943",
publisher = "Georg Thieme Verlag",
number = "12",

}

TY - JOUR

T1 - Relaxant Effects of Flavonoids in Isolated Guinea Pig Trachea and Their Structure-Activity Relationships

AU - Ko, Wun-Chang

AU - Liu, Pi Ying

AU - Chen, Junn Lain

AU - Leu, I. Jung

AU - Shih, Chwen Ming

PY - 2003/12

Y1 - 2003/12

N2 - The structure-activity relationships between flavonoids and their tracheal relaxant action are little known. In the present study, 26 natural and synthetic flavonoids, divided into the five classes of flavones, flavonols, flavanones, isoflavones, and chalcones, were tested, and their IC50 values were determined. The IC50 values of these five classes indicated that flavones were more potent than flavonols. Flavones were also more potent than flavanones suggesting that the presence of a double bond between C-2 and C-3 is important. However, flavones were similar to isoflavones in potency. Chalcones, a class with an open C-ring, appeared to be the least potent among these five classes. Introduction of a hydroxy group at position C-6 of flavones increases their relaxant activities. So does adding a hydroxy group at position C-7 of flavones. It appears that the optimal number of hydroxy groups introduced to the A-ring of flavones is one. As more hydroxy groups are introduced to positions at C-5, C-6, and/or C-7 of flavones, the IC50 values increase. It seems that flavones or flavonols with a pyrogallol moiety either in the A- or B-ring, respectively, have no activity. It appears that flavonols with ortho-hydroxy groups in the B-ring are more potent than those with meta-hydroxy groups. The activity of 6-hydroxyflavone disappears if the C-6 hydroxy group of the A-ring is methoxylated. If the C-4′ hydroxy group of the B ring is methoxylated, the relaxant effect of these flavones is also attenuated or disappears. Therefore, the hydroxy group on either the A- or B-ring of flavones and flavonols being methylated resulted in lower potency of the tracheal relaxant effects. However, when all hydroxy groups on both the A- and B-rings of flavones or flavonols are methoxylated this results in higher potency. Therefore, the influence of methoxylation in flavones may be similar to that in flavonols. However, if the C-3 hydroxy group on the C-ring of flavonols, but not flavones which lack this hydroxy group, is methoxylated, the relaxant effects may increase. Glycosylation of the hydroxy group at position C-7 of flavones or flavanones attenuates the relaxant effects.

AB - The structure-activity relationships between flavonoids and their tracheal relaxant action are little known. In the present study, 26 natural and synthetic flavonoids, divided into the five classes of flavones, flavonols, flavanones, isoflavones, and chalcones, were tested, and their IC50 values were determined. The IC50 values of these five classes indicated that flavones were more potent than flavonols. Flavones were also more potent than flavanones suggesting that the presence of a double bond between C-2 and C-3 is important. However, flavones were similar to isoflavones in potency. Chalcones, a class with an open C-ring, appeared to be the least potent among these five classes. Introduction of a hydroxy group at position C-6 of flavones increases their relaxant activities. So does adding a hydroxy group at position C-7 of flavones. It appears that the optimal number of hydroxy groups introduced to the A-ring of flavones is one. As more hydroxy groups are introduced to positions at C-5, C-6, and/or C-7 of flavones, the IC50 values increase. It seems that flavones or flavonols with a pyrogallol moiety either in the A- or B-ring, respectively, have no activity. It appears that flavonols with ortho-hydroxy groups in the B-ring are more potent than those with meta-hydroxy groups. The activity of 6-hydroxyflavone disappears if the C-6 hydroxy group of the A-ring is methoxylated. If the C-4′ hydroxy group of the B ring is methoxylated, the relaxant effect of these flavones is also attenuated or disappears. Therefore, the hydroxy group on either the A- or B-ring of flavones and flavonols being methylated resulted in lower potency of the tracheal relaxant effects. However, when all hydroxy groups on both the A- and B-rings of flavones or flavonols are methoxylated this results in higher potency. Therefore, the influence of methoxylation in flavones may be similar to that in flavonols. However, if the C-3 hydroxy group on the C-ring of flavonols, but not flavones which lack this hydroxy group, is methoxylated, the relaxant effects may increase. Glycosylation of the hydroxy group at position C-7 of flavones or flavanones attenuates the relaxant effects.

KW - Flavones

KW - Flavonoids

KW - Flavonols

KW - Guinea pig

KW - Isoflavone

KW - Structure-activity relationships

KW - Tracheal relaxant

UR - http://www.scopus.com/inward/record.url?scp=1242284439&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1242284439&partnerID=8YFLogxK

U2 - 10.1055/s-2003-45187

DO - 10.1055/s-2003-45187

M3 - Article

C2 - 14750022

AN - SCOPUS:1242284439

VL - 69

SP - 1086

EP - 1090

JO - Planta Medica

JF - Planta Medica

SN - 0032-0943

IS - 12

ER -