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

Saftić, Dijana; Studzińska, Mirosława; Paradowska, Edyta; Piantanida, Ivo; Baranović, Goran; Białek-Pietras, Magdalena; Leśnikowski, Zbigniew J. (2020) 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. Bioorganic Chemistry, 94 . ISSN 0045-2068

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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.

Item Type:	Article
Uncontrolled Keywords:	antivirals ; uridine ; nucleoside analogues, boron clusters, isomerism
Subjects:	NATURAL SCIENCES > Chemistry NATURAL SCIENCES > Chemistry > Organic Chemistry
Divisions:	Division of Organic Chemistry and Biochemistry
Projects:	Project title Project leader Project code Project type Oligo-Derivative Composites of Nucleic Acids and Boron Clusters – a New Material for Bionanotechnology Zbigniew J. Leśnikowski 015/16/W/ST5/00413 NSC Poland
Depositing User:	Dijana Pavlović Saftić
Date Deposited:	02 Sep 2022 12:41
URI:	http://fulir.irb.hr/id/eprint/7539
DOI:	10.1016/j.bioorg.2019.103466

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