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


Journal

ChemMedChem
ISSN: 1860-7187
Titre abrégé: ChemMedChem
Pays: Germany
ID NLM: 101259013

Informations de publication

Date de publication:
07 01 2020
Historique:
received: 23 09 2019
revised: 30 10 2019
pubmed: 20 11 2019
medline: 29 1 2021
entrez: 20 11 2019
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 31743599
doi: 10.1002/cmdc.201900542
doi:

Substances chimiques

Liposomes 0
Octanols 0
Pyridines 0
pyridoclax 0
Water 059QF0KO0R

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

136-154

Informations de copyright

© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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Auteurs

Martina De Pascale (M)

Normandie Univ, UniCaen, CERMN, 14000, Caen, France.

Domenico Iacopetta (D)

Department of Pharmacy Health and Nutritional Sciences, University of Calabria, 87036, Arcavacata di Rende, Italy.

Marc Since (M)

Normandie Univ, UniCaen, CERMN, 14000, Caen, France.

Sophie Corvaisier (S)

Normandie Univ, UniCaen, CERMN, 14000, Caen, France.

Véronique Vie (V)

Département Matière Molle BioMolécules aux Interfaces Fluides IPR, UR1, Campus de Beaulieu, 35042, Rennes Cedex, France.

Gilles Paboeuf (G)

Département Matière Molle BioMolécules aux Interfaces Fluides IPR, UR1, Campus de Beaulieu, 35042, Rennes Cedex, France.

Didier Hennequin (D)

Normandie Univ UniCaen ABTE, 14000, Caen, France.

Serge Perato (S)

Normandie Univ, UniCaen, CERMN, 14000, Caen, France.

Marcella De Giorgi (M)

Normandie Univ, UniCaen, CERMN, 14000, Caen, France.

Maria Stefania Sinicropi (MS)

Department of Pharmacy Health and Nutritional Sciences, University of Calabria, 87036, Arcavacata di Rende, Italy.

Jana Sopkova-De Oliveira Santos (J)

Normandie Univ, UniCaen, CERMN, 14000, Caen, France.

Anne-Sophie Voisin-Chiret (AS)

Normandie Univ, UniCaen, CERMN, 14000, Caen, France.

Aurélie Malzert-Freon (A)

Normandie Univ, UniCaen, CERMN, 14000, Caen, France.

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Classifications MeSH