Synthesis of Pyridoclax Analogues: Insight into Their Druggability by Investigating Their Physicochemical Properties and Interactions with Membranes

Autor: Sophie Corvaisier, Martina De Pascale, Véronique Vié, Marcella De Giorgi, Aurélie Malzert-Fréon, Serge Perato, Maria Stefania Sinicropi, Domenico Iacopetta, Anne Sophie Voisin-Chiret, Jana Sopkova-de Oliveira Santos, Gilles Paboeuf, Didier Hennequin, Marc Since
Přispěvatelé: Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Università della Calabria [Arcavacata di Rende] (Unical), Institut de Physique de Rennes (IPR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Aliments Bioprocédés Toxicologie Environnements (ABTE), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Ligue Contre le Cancer (National committee), 'Ligue Contre le Cancer' (Calvados committee), Commissione Europea, Fondo Sociale Europeo (FSE 2007/2013-PROGRAMMA ARUE), Regione Calabria, Region Normandie, European Union via the European Regional Development Fund (FEDER), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Drug
Octanols
Pyridines
media_common.quotation_subject
Druggability
membrane models
[CHIM.THER]Chemical Sciences/Medicinal Chemistry
Microscopy
Atomic Force
01 natural sciences
Biochemistry
Structure-Activity Relationship
Analytical methods
medicinal chemistry
Drug Discovery
General Pharmacology
Toxicology and Pharmaceutics
media_common
Pharmacology
Liposome
010405 organic chemistry
Chemistry
Organic Chemistry
structure-activity relationships
Water
Hydrogen Bonding
oligopyridines
Anticancer drug
0104 chemical sciences
3. Good health
Kinetics
010404 medicinal & biomolecular chemistry
Spectrometry
Fluorescence
Membrane
Solubility
Drug development
Liposomes
Biophysics
[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology
Molecular Medicine
Hydrophobic and Hydrophilic Interactions
Zdroj: ChemMedChem
ChemMedChem, Wiley-VCH Verlag, 2020, 15 (1), pp.136-154. ⟨10.1002/cmdc.201900542⟩
ChemMedChem, 2020, 15 (1), pp.136-154. ⟨10.1002/cmdc.201900542⟩
ISSN: 1860-7179
1860-7187
DOI: 10.1002/cmdc.201900542⟩
Popis: International audience; Pyridoclax is considered a promising anticancer drug, acting as a protein-protein interaction disruptor, with potential applications in the treatment of ovarian, lung, and mesothelioma cancers. Eighteen sensibly selected structural analogues of Pyridoclax were synthesized, and their physicochemical properties were systematically assessed and analyzed. Moreover, considering that drug-membrane interactions play an essential role in understanding the mode of action of a given drug and its eventual toxic effects, membrane models were used to investigate such interactions in bulk (liposomes) and at the air-water interface. The measured experimental data on all original oligopyridines allowed the assessment of relative differences in terms of physicochemical properties, which could be determinant for their druggability, and hence for drug development.
Databáze: OpenAIRE
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