Benzouracil-coumarin-arene conjugates as inhibiting agents for chikungunya virus
Hwu, Jih Ru × Kapoor, Mohit Tsay, Shwu-Chen Lin, Chun-Cheng Hwang, Kuo Chu Horng, Jia-Cherng Chen, I-Chia Shieh, Fa-Kuen Leyssen, Pieter Neyts, Johan #
Antiviral Research vol:118 pages:103-109
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.