Synthesis and in vitro antioxidant activity of glycyrrhetinic acid derivatives tested with the cytochrome P450/NADPH system

Mourboul Ablise, Brigitte Leininger-Muller, DalWoong Choi, Gérard Siest, Vincent Loppinet, Sophie Visvikis

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Five glycyrrhetinic acid (Ib) derivatives have been synthesized to try to improve the antioxidant activity. Their in vitro antioxidant activities were studied using a cytochrome P450/NADPH reductase system from rat liver microsomes. The generation of microsomal free radicals was followed by oxidation of the DCFH-DA probe, while evaluating the capacity to inhibit reactive oxygen species (ROS) formation. Two hydroxylated derivatives, 18β-olean-12-ene- 3β,11α,30-triol (II) and 18β-olean-12-ene-3β,11β,30- triol (IV), exhibited strong antioxidant activities. At a concentration of 1.0 mg/ml, these derivatives inhibited ROS formation by 50% and 51%, respectively. Moreover, two homo- and heterocyclic diene derivatives, 18β-olean-11,13(18) -diene-3β,30-diol (III) and 18β-olean-9(11),12-diene-3β,30-diol (V), were also effective in ROS-scavenging activity (inhibition of 41% and 44% of ROS activity, respectively). In the same conditions, the lead compound (Ib) and the reference vitamin E inhibited ROS activity by 31% and 32%, respectively. Our results suggest that the chemical reduction of the 11-keto and 30-carboxyl groups into hydroxyl function (example, II, IV) can increase the antioxidant activity of Ib significantly. In view of these results, our study represents a further approach to the development of potential therapeutic agents from Ib derivatives for use in pathologic events in which, free radical damage could be involved.

Original languageEnglish
Pages (from-to)1436-1439
Number of pages4
JournalChemical and Pharmaceutical Bulletin
Volume52
Issue number12
DOIs
Publication statusPublished - 2004 Dec 1
Externally publishedYes

Fingerprint

Glycyrrhetinic Acid
NADP
Cytochrome P-450 Enzyme System
Reactive Oxygen Species
Antioxidants
Derivatives
Free Radicals
Lead compounds
NADPH-Ferrihemoprotein Reductase
Scavenging
Liver Microsomes
Vitamin E
Hydroxyl Radical
Liver
Rats
In Vitro Techniques
Oxidation

ASJC Scopus subject areas

  • Chemistry(all)
  • Organic Chemistry
  • Drug Discovery
  • Pharmacology

Cite this

Synthesis and in vitro antioxidant activity of glycyrrhetinic acid derivatives tested with the cytochrome P450/NADPH system. / Ablise, Mourboul; Leininger-Muller, Brigitte; Choi, DalWoong; Siest, Gérard; Loppinet, Vincent; Visvikis, Sophie.

In: Chemical and Pharmaceutical Bulletin, Vol. 52, No. 12, 01.12.2004, p. 1436-1439.

Research output: Contribution to journalArticle

Ablise, Mourboul ; Leininger-Muller, Brigitte ; Choi, DalWoong ; Siest, Gérard ; Loppinet, Vincent ; Visvikis, Sophie. / Synthesis and in vitro antioxidant activity of glycyrrhetinic acid derivatives tested with the cytochrome P450/NADPH system. In: Chemical and Pharmaceutical Bulletin. 2004 ; Vol. 52, No. 12. pp. 1436-1439.
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