title: Benzouracil-coumarin-arene conjugates as inhibiting agents for chikungunya virus.
abstract: 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 = 10.2-19.1 μM) and showed low toxicity (CC50 = 75.2-178 μM). 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.
authors.affiliation: Department of Chemistry & Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan; Department of Chemistry, National Central University, Jhongli City 32001, Taiwan. Electronic address: jrhwu@mx.nthu.edu.tw.
authors.forename: Jih Ru
authors.initials: JR
authors.lastname: Hwu
authors.affiliation: Department of Chemistry & Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan.
authors.forename: Mohit
authors.initials: M
authors.lastname: Kapoor
authors.affiliation: Department of Chemistry, National Central University, Jhongli City 32001, Taiwan. Electronic address: tsay.susan@gmail.com.
authors.forename: Shwu-Chen
authors.initials: SC
authors.lastname: Tsay
authors.affiliation: Department of Chemistry & Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan.
authors.forename: Chun-Cheng
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Department of Chemistry & Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan.
authors.forename: Kuo Chu
authors.initials: KC
authors.lastname: Hwang
authors.affiliation: Department of Chemistry & Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan.
authors.forename: Jia-Cherng
authors.initials: JC
authors.lastname: Horng
authors.affiliation: Department of Chemistry & Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan.
authors.forename: I-Chia
authors.initials: IC
authors.lastname: Chen
authors.affiliation: Department of Chemistry, National Central University, Jhongli City 32001, Taiwan.
authors.forename: Fa-Kuen
authors.initials: FK
authors.lastname: Shieh
authors.affiliation: Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Leyssen
authors.affiliation: Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium. Electronic address: johan.neyts@rega.kuleuven.be.
authors.forename: Johan
authors.initials: J
authors.lastname: Neyts
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002646:Chikungunya virus / Q000187:drug effects*; D002522:Chlorocebus aethiops; D003374:Coumarins / Q000138:chemical synthesis / Q000494:pharmacology*; D006841:Hydrocarbons, Aromatic / Q000138:chemical synthesis / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013057:Spectrum Analysis; D013329:Structure-Activity Relationship; D014498:Uracil / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology*; D014709:Vero Cells
chemical_list: D000998:Antiviral Agents; D003374:Coumarins; D006841:Hydrocarbons, Aromatic; D014498:Uracil
keywords: Benzouracil; Chikungunya virus; Conjugate; Coumarin; Sulfonate ester; Thiomethylene