Synthesis and in vitro antiviral activity of lipophilic pyrimidine nucleoside/carborane conjugates

• Novel para-carborane/uridine conjugates via Sonogashira coupling were synthesized.
• The cytotoxicity and antiviral activity of the obtained compounds was tested.
• Two highly active against HCMV derivatives have been identified.
• An unusual specificity of the conjugates towards HCMV was discovered.

A series of novel conjugates of para-carborane with 5-ethynyl-uridine or 2′-deoxyuridine were synthesized. The conjugates were prepared by Sonogashira coupling of para-carborane terminal alkynes and 5-iodo-nucleoside. The designed compounds demonstrated low to moderate cytotoxicity in several cell lines. The antiviral activities of the agents were measured against a panel of DNA and RNA viruses. The most potent compound reported is 5-[(1,12-dicarba-closo-dodecaboran-2-yl)ethyn-1-yl]-2′-deoxyuridine (8), with an IC50 value of 5.5 μM and a selectivity index higher than 180. This compound is unusual in that it exhibits antiviral activity against HCMV and is not active against HSV-1, HPIV-3 or EMCV.

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