Chikungunya virus inhibition by synthetic coumarin-guanosine conjugates.
Basic Information
ID: ALA4400522
Journal: Eur J Med Chem
Title: Chikungunya virus inhibition by synthetic coumarin-guanosine conjugates.
Authors: Hwu JR, Huang WC, Lin SY, Tan KT, Hu YC, Shieh FK, Bachurin SO, Ustyugov A, Tsay SC.
Abstract: 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.
CiteXplore: 30703657
DOI: 10.1016/j.ejmech.2019.01.037
Patent ID: ┄