Structure-activity relationship study of arbidol derivatives as inhibitors of Chikungunya virus replication
Autor(es): Di Mola Antonia, Peduto Antonella, La Gatta Annalisa, Delang Leen, Pastorino Boris, Neyts Johan, Leyssen Pieter, de Rosa Mario, Filosa Rosanna
Resumo: Chikungunya virus (CHIKV), a mosquito-borne arthrogenic Alphavirus, causes an acute febrile illness in humans, that is, accompanied by severe joint pains. In many cases, the infection leads to persistent arthralgia, which may last for weeks to several years. The re-emergence of this infection in the early 2000s was exemplified by numerous outbreaks in the eastern hemisphere. Since then, the virus is rapidly spreading. Currently, no drugs have been approved or are in development for the treatment of CHIKV, which makes this viral infection particularly interesting for academic medicinal chemistry efforts. Several molecules have already been identified that inhibit CHIKV replication in phenotypic virus-cell-based assays. One of these is arbidol, a molecule that already has been licensed for the treatment of influenza A - B virus infections. For structural optimization, a dedicated libraries of 43 indole-based derivatives were evaluated leading to more potent analogues (IIIe - IIIf) with anti-chikungunya virus (CHIKV) activities higher than those of the other derivatives, including the lead compound, - with a selective index of inhibition 13.2 - 14.6, respectively, higher than that of ARB (4.6).
Palavras-Chave: Arbidol; Chikungunya virus; Indoles
Imprenta: Bioorganic & Medicinal Chemistry, v. 22, n. 21, p. 6014-6025, 2014
Identificador do objeto digital: 10.1016/j.bmc.2014.09.013
Descritores: Chikungunya virus - Cell ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Chikungunya fever ; Chikungunya virus - Public health
Data de publicação: 2014
