Antiviral and Apoptosis Modulating Potential of Fluorinated Compounds

In our laboratory, we focus on the design, synthesis, and evaluation of fluorinated compounds that could be used in the tretament of diseases caused by the Epstein-Barr virus (EBV) and virus vesicular stomatitis (VVS). EBV is a DNA-containing virus. It is characterized by an acute form of infection as well as a latent form, which may lead to cell transformation and to cancer (lymphoma, carcinoma). VVS is a RNA-containing virus.

For this purpose, in a first step, we used the PASS software by which we could identify potential antiviral candidates among which a fluorinated derivative of uracil (G27), a trifluoromethyl-substituted derivative of a thiosugar (SBIO6), a bisphosphonic acid (10s19) and several derivatives of alanin and glucose (10s20 - 10s28).

Our in vitro studies revealed an antiviral activity for a few compounds. Three compounds appeared to be effective against EBV: G27 (EC₅₀ = 100 µg/ml), 10s20 (EC₅₀ =  µg/ml), and 10s25 (EC₅₀ <62 µg/ml, replication of EBV was suppressed at 100 % at a concentration of 62 µg/ml). The ability to inhibit reproduction of VVS was showed for compound 10s19 (EC₅₀ = 19 µg/ml) and for compound 10s24 (EC₅₀ = 29 µg/ml). It was established that the index of selectivity for these compounds ranged from 10 to 100.

As Epstein-Barr virus (EBV) is the cause of several lymphoproliferative diseases, we studied the potency of G27 and SBIO6 compounds to make an apoptosis induction. Apoptotic cells were detected using a flow cytometry. Addition of G27 led to the observation of two peaks in the histogram, what may indicate a break of the cell cycle by this compound. It was also established that by addition of SBIO6 the percentage of apoptotic cells was significantly increased when compared to the control and reached 70 - 90 percent.