Note of Caution for the Aqueous Behaviour of Metal‐Based Drug Candidates

Autor: Anna Notaro, Annie Castonguay, Gilles Gasser
Přispěvatelé: Institute of Chemistry for Life and Health Sciences (iCLeHS), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), This work was financially supported by an ERC Consolidator Grant PhotoMedMet to G.G. (GA 681679) and has received support under the program Investissements d'Avenir launched by the French Government and implemented by the ANR with the reference ANR-10-IDEX-0001-02 PSL (G.G.). Ile de France Region is gratefully acknowledged for financial support of 500 MHz NMR spectrometer of Chimie ParisTech in the framework of the SESAME equipment project. We acknowledge the loan of Agilent's equipment to Chimie ParisTech. This work was also supported by INRS University, the Natural Sciences and Engineering Research Council of Canada (Discovery 06336 to A.C.), the Fonds de Recherche du Québec Santé (Junior 1 Research Scholar, Établissement de Jeunes Chercheurs 32622 to A.C.) and the Canada Foundation for Innovation (John Evans Leaders Fund 34846 to A.C.)., ANR-10-IDEX-0001,PSL,Paris Sciences et Lettres(2010), European Project: 681679, H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC),681679,PhotoMedMet(2017)
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Drug
media_common.quotation_subject
[SDV]Life Sciences [q-bio]
Inorganic chemistry
MESH: Molecular Structure
chemistry.chemical_element
Antineoplastic Agents
01 natural sciences
Biochemistry
Metal
bioinorganic chemistry
Colloid
Microscopy
Electron
Transmission
Coordination Complexes
MESH: Coordination Complexes
Neoplasms
Drug Discovery
Aqueous solubility
MESH: Water
Humans
cancer
MESH: Neoplasms
General Pharmacology
Toxicology and Pharmaceutics
ruthenium
medicinal inorganic chemistry
media_common
Pharmacology
Aqueous solution
MESH: Humans
Molecular Structure
010405 organic chemistry
Organic solvent
Organic Chemistry
Water
aqueous behaviour
MESH: Ruthenium
0104 chemical sciences
Ruthenium
010404 medicinal & biomolecular chemistry
chemistry
visual_art
visual_art.visual_art_medium
MESH: Microscopy
Electron
Transmission
Molecular Medicine
MESH: Antineoplastic Agents
Zdroj: ChemMedChem
ChemMedChem, 2020, 15 (4), pp.345-348. ⟨10.1002/cmdc.201900677⟩
ISSN: 1860-7179
1860-7187
DOI: 10.1002/cmdc.201900677⟩
Popis: International audience; Poor aqueous solubility is one of the recurrent drawbacks of many compounds in medicinal chemistry. To overcome this limitation, the dilution of drug candidates from stock solutions of an organic solvent is common practice. However, the precise characterisation of these compounds in aqueous solutions is often neglected, leading to some uncertainties regarding the nature of the actual active species. In this communication, we demonstrate that two ruthenium complexes previously reported by our group for their chemotherapeutic potential against cancer, namely [Ru(DIP)2 (sq)](PF6 ) and [Ru(DIP)2 (3-methoxysq)](PF6 ), where DIP is 4,7-diphenyl-1,10-phenanthroline, sq=semiquinonate and 3-methoxysq=3-methoxysemiquinonate, form colloids in water-DMSO (1 % v/v) mixtures that are invisible to the naked eyes. [Ru(DIP)2 (3-methoxysq)](PF6 ) was found to form a highly stable and monodispersed colloid with nanoaggregates of ∼25 nm. In contrast, [Ru(DIP)2 (sq)](PF6 ) was found to form large reticulates of mostly spherical aggregates which size was found to increase over time. The difference in size and shape distribution of drug candidates is of tremendous significance as the study of their biological activity might be severely affected. Overall, we strongly believe that these observations should be taken into account by the scientific community working on the development of metal-based drugs with poor water solubility.
Databáze: OpenAIRE
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