2. Academic Validation
  3. New and promising type of leukotriene B4 (LTB4) antagonists based on the 1,4-benzodioxine structure

New and promising type of leukotriene B4 (LTB4) antagonists based on the 1,4-benzodioxine structure

  • Eur J Med Chem. 2023 Apr 6;254:115332. doi: 10.1016/j.ejmech.2023.115332.
Latifa Bouissane 1,  Mostafa Khouili 2,  Gérard Coudert 3,  M Dolors Pujol 4,  Gérald Guillaumet 5
Affiliations

Affiliations

  • 1 Molecular Chemistry, Materials and Catalysis Laboratory, Faculty of Sciences and Technologies, Sultan Moulay Slimane University, BP 523, 23000, Beni-Mellal, Morocco. Electronic address: [email protected].
  • 2 Molecular Chemistry, Materials and Catalysis Laboratory, Faculty of Sciences and Technologies, Sultan Moulay Slimane University, BP 523, 23000, Beni-Mellal, Morocco. Electronic address: [email protected].
  • 3 Institut de Chimie Organique et Analytique (ICOA), Université d'Orléans. UMR CNRS 7311, rue de Chartres, BP-6759, 45067, Orléans, France.
  • 4 Laboratori de Química Farmacèutica, Facultat de Farmàcia i Ciències de l'Alimentació, Universitat de Barcelona, Av. Joan XXIII, 27-31, 08028, Barcelona, Spain.
  • 5 Institut de Chimie Organique et Analytique (ICOA), Université d'Orléans. UMR CNRS 7311, rue de Chartres, BP-6759, 45067, Orléans, France. Electronic address: [email protected].
PMID: 37043995 DOI: 10.1016/j.ejmech.2023.115332
Abstract

New leukotriene B4 (LTB4) antagonists have been synthesized that can be considered as potential anti-inflammatory drugs. Structures containing the dioxygenated nucleus of 1,4-benzodioxine constitute a potential group of leukotriene B4 (LTB4) antagonists. The objective of this study was to access efficient and selective LTB4 antagonists as a way to elucidate the role of LTB4 in inflammatory processes and therefore allow the development of new types of structures based on 1,4-benzodioxine. Forty-one new 1,4-benzodioxine molecules substituted at different positions of the heterocyclic nucleus were synthesized to determine the minimum structural requirements by studying structure-activity relationships. Eighteen of them were tested in vitro and in vivo for their anti-inflammatory activity related to the antagonist character of LTB4. Pharmacological tests have shown satisfactory in vitro activity for compounds 24b, 24c and 24e with IC50's of 288, 439, 477 nM respectively. The results of the in vivo tests, carried out with the compound that presented greater activity in the in vitro tests 24b, have shown significant anti-inflammatory properties.

Keywords

1,4-Benzodioxine; Anti-inflammatory properties; Carrageenan edema test; Inflammation; Leukotriene B4 (LTB4) antagonists.

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