Note of Caution for the Aqueous Behaviour of Metal-Based Drug Candidates.
ChemMedChem
; 15(4): 345-348, 2020 02 17.
Article
em En
| MEDLINE
| ID: mdl-31840945
ABSTRACT
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 â¼25â
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Rutênio
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Água
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Complexos de Coordenação
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Neoplasias
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Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
ChemMedChem
Assunto da revista:
FARMACOLOGIA
/
QUIMICA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
França