Research paperChikungunya virus inhibition by synthetic coumarin–Guanosine (cas 118-00-3) conjugates

Add time:08/29/2019    Source:sciencedirect.com

Since its discovery in Tanganyika, Africa in 1952, chikungunya virus (CHIKV) outbreaks have occurred in Africa, Asia, Europe, and America. Till now chikungunya fever has spread in nearly 40 countries. Because of lack of effective vaccines and antiviral drugs to intervene this disease, 21 new conjugated compounds were designed and synthesized by coupling of 6,8-dithioguanosine at its C-6 position with 3-(chloromethyl)coumarins bearing an F, Cl, Br, Me, or –OMe substituent through the –SCH2– joint. Meanwhile, an organic “dummy” ligand (e.g., methyl, benzyl, and naphthylmethyl) or a coumarinyl moiety was attached at the C-8 position. By high through-put screening, three of these new conjugates were found to inhibit CHIKV in Vero cells with significant potency (EC50 = 9.9–13.9 μM) and showed low toxicity (CC50 = 96.5–212 μM). The selectivity index values were 9.37–21.7. Their structure–activity relationship was deduced, which indicates that the coumarin moiety is essential and the presence of a –OMe group enhances the antiviral activity.

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