Comparative study of the effects of ortho-, meta- and para-carboranes (C2B10H12) on the physicochemical properties, cytotoxicity and antiviral activity of uridine and 2'-deoxyuridine boron cluster conjugates.
Bioorg Chem
; 94: 103466, 2020 01.
Article
em En
| MEDLINE
| ID: mdl-31826808
ABSTRACT
In this study, a series of uridine (U) and 2'-deoxyuridine (dU) conjugates containing an isomeric ortho-, meta- or para-carborane cluster (C2B10H12) attached at C-5 through an ethynyl linker were synthesized. The effect of carborane cluster isomerism on the conjugate syn/anti conformation, molar extinction coefficient, lipophilicity, susceptibility to phosphorylation (by TK1, TK2 and dCK), cytotoxicity and antiviral activity was evaluated. A strong effect of the boron cluster modification on the syn/anti equilibrium of the modified nucleosides was observed. An increase in lipophilicity compared with unmodified U and dU, especially for conjugates bearing a para-carborane cluster, was detected. Furthermore a pronounced and differential influence of the boron cluster modification on the electronic properties of the nucleobase chromophore was observed. The obtained conjugates have low or medium toxicity toward several cell lines, are phosphorylated fairly well by TK1 and are poor or not substrates for dCK. Furthermore, the conjugates preferentially inhibit HCMV replication with an SI index as high as 22 for the ortho-carborane derivative of U and more than 180 for the para-carborane derivative of dU.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antivirais
/
Vírus de RNA
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Uridina
/
Boranos
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Vírus de DNA
Limite:
Humans
Idioma:
En
Revista:
Bioorg Chem
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Polônia