Benzouracil-coumarin-arene conjugates as inhibiting agents for chikungunya virus

Chikungunya virus (CHIKV) is an arbovirus that was first recognized in an epidemic form in East Africa in 1952-1953. The virus is primarily transmitted through mosquitoes and the resulting disease, chikungunya fever, is found in nearly 40 countries. Neither an effective vaccine nor a specific antiviral drug exists for treatments of chikungunya fever. Thus 22 new conjugated compounds of uracil-coumarin-arene were designed and synthesized as potential inhibiting agents. Their chemical structures were determined unambiguously by spectroscopic methods, including single-crystal X-ray diffraction crystallography. The three units in these conjugates were connected by specially designed -SCH2- and -OSO2- joints. Five of these new conjugates were found to inhibit CHIKV in Vero cells with significant potency (EC50=10.2-19.1μM) and showed low toxicity (CC50=75.2-178μM). The selective index values were 8.8-11.5 for three conjugates. By analysis of the data from the anti-viral assays, the structure-activity relationship is derived on the basis of the nature of the uracil, the functional groups attached to the arene, and the joints between the ring units.publisher: Elsevier articletitle: Benzouracil–coumarin–arene conjugates as inhibiting agents for chikungunya virus journaltitle: Antiviral Research articlelink: http://dx.doi.org/10.1016/j.antiviral.2015.03.013 content_type: article copyright: Copyright © 2015 Elsevier B.V. All rights reserved.status: publishe