2. Academic Validation
  3. Damsin and neoambrosin: Two sesquiterpene lactones with affinity and different activity for PPAR and TRPA1 receptors

Damsin and neoambrosin: Two sesquiterpene lactones with affinity and different activity for PPAR and TRPA1 receptors

  • Bioorg Chem. 2025 Jan:154:108032. doi: 10.1016/j.bioorg.2024.108032.
Shymaa I A Abdel-Dayem 1,  Asmaa M Otify 2,  Fabio Arturo Iannotti 3,  Fatema R Saber 4,  Aniello Schiano Moriello 5,  Simone Giovannuzzi 6,  Łukasz Świątek 7,  Alessandro Bonardi 8,  Paola Gratteri 9,  Krystyna Skalicka-Woźniak 10,  Claudiu T Supuran 11
Affiliations

Affiliations

  • 1 Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini, Cairo 11562, Egypt. Electronic address: [email protected].
  • 2 Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini, Cairo 11562, Egypt. Electronic address: [email protected].
  • 3 Institute of Biomolecular Chemistry, National Research Council (ICB-CNR), Via Campi Flegrei 34, 80078 Pozzuoli, NA, Italy. Electronic address: [email protected].
  • 4 Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini, Cairo 11562, Egypt. Electronic address: [email protected].
  • 5 Institute of Biomolecular Chemistry, National Research Council (ICB-CNR), Via Campi Flegrei 34, 80078 Pozzuoli, NA, Italy. Electronic address: [email protected].
  • 6 NEUROFARBA Department, Pharmaceutical and Nutraceutical Section and Laboratory of Molecular Modeling Cheminformatics & QSAR, University of Florence, Via U. Schiff 6, Sesto Fiorentino, Florence 50019, Italy. Electronic address: [email protected].
  • 7 Department of Virology with Viral Diagnostics Laboratory, Medical University of Lublin, 20-093 Lublin, Poland. Electronic address: [email protected].
  • 8 NEUROFARBA Department, Pharmaceutical and Nutraceutical Section and Laboratory of Molecular Modeling Cheminformatics & QSAR, University of Florence, Via U. Schiff 6, Sesto Fiorentino, Florence 50019, Italy. Electronic address: [email protected].
  • 9 NEUROFARBA Department, Pharmaceutical and Nutraceutical Section and Laboratory of Molecular Modeling Cheminformatics & QSAR, University of Florence, Via U. Schiff 6, Sesto Fiorentino, Florence 50019, Italy. Electronic address: [email protected].
  • 10 Department of Chemistry of Natural Products, Medical University of Lublin, 20-093 Lublin, Poland. Electronic address: [email protected].
  • 11 NEUROFARBA Department, Pharmaceutical and Nutraceutical Section and Laboratory of Molecular Modeling Cheminformatics & QSAR, University of Florence, Via U. Schiff 6, Sesto Fiorentino, Florence 50019, Italy. Electronic address: [email protected].
PMID: 39672074 DOI: 10.1016/j.bioorg.2024.108032
Abstract

Ambrosia maritima L. (family Asteraceae) is an annual herb widely distributed throughout the Mediterranean region and Africa. The herb is employed in folk medicine for the treatment of many ailments. Herein, we report a comprehensive investigation of the diverse biological potential of two sesquiterpene lactones, damsin and neoambrosin, isolated from Ambrosia maritima. 1D and 2D NMR and HR-ESI-MS/MS were employed to characterize the chemical structures of both compounds. In order to identify biological targets of both compounds we investigated their potential affinity for peroxisome proliferator-activated receptors (PPARs) and transient receptor potential (TRP) channels, which are pleiotropic classes of receptors implicated in essential functions of the body. This was investigated using a luciferase assay and a calcium fluorometric assay. A Carbonic Anhydrase inhibition assay was also performed using stopped flow CO2 hydrase spectrophotometric assay. Our analysis revealed that unlike damsin, neoambrosin showed a selective partial agonist effect on PPARγ receptors and TRPA1 channels. Its binding mode was investigated through in silico analysis. Both compounds showed no affinity for the tested carbonic anhydrases. Overall, our study details the chemical properties of neoambrosin and damsin and highlights neoambrosin as novel, cost-effective partial agonist of PPARɣ and TRPA1 receptors despite additional in vivo studies are needed to elucidate its biological and pharmacological properties.

Keywords

Ambrosia maritima; Carbonic anhydrase; Damsin; Molecular docking; Neoambrosin; PPAR; TRPA1.

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