title: Structure-activity relationship study of arbidol derivatives as inhibitors of chikungunya virus replication.
abstract: 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 and B virus infections. For structural optimization, a dedicated libraries of 43 indole-based derivatives were evaluated leading to more potent analogues (IIIe and IIIf) with anti-chikungunya virus (CHIKV) activities higher than those of the other derivatives, including the lead compound, and with a selective index of inhibition 13.2 and 14.6, respectively, higher than that of ARB (4.6).
authors.affiliation: Department of Experimental Medicine, University of Naples, Via Costantinopoli, 16, 80138 Naples, Italy.
authors.forename: Antonia
authors.initials: A
authors.lastname: Di Mola
authors.affiliation: Department of Experimental Medicine, University of Naples, Via Costantinopoli, 16, 80138 Naples, Italy; Dermofarma, Via Cortenocera, 82030 S. Salvatore Telesino (BN), Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Peduto
authors.affiliation: Department of Experimental Medicine, University of Naples, Via Costantinopoli, 16, 80138 Naples, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: La Gatta
authors.affiliation: Laboratory of Virology and Experimental Chemotherapy, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
authors.forename: Leen
authors.initials: L
authors.lastname: Delang
authors.affiliation: UMR 190 'Emergence des Pathologies Virales', Aix-Marseille Univ., IRD French Institute of Research for Development, EHESP French School of Public Health, Marseille, France.
authors.forename: Boris
authors.initials: B
authors.lastname: Pastorino
authors.affiliation: Laboratory of Virology and Experimental Chemotherapy, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Neyts
authors.affiliation: Laboratory of Virology and Experimental Chemotherapy, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Leyssen
authors.affiliation: Department of Experimental Medicine, University of Naples, Via Costantinopoli, 16, 80138 Naples, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: de Rosa
authors.affiliation: Department of Experimental Medicine, University of Naples, Via Costantinopoli, 16, 80138 Naples, Italy. Electronic address: rosanna.filosa@unina2.it.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Filosa
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D065632:Chikungunya Fever / Q000188:drug therapy*; D002646:Chikungunya virus / Q000187:drug effects* / Q000502:physiology; D002522:Chlorocebus aethiops; D006801:Humans; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects*; D013440:Sulfides
chemical_list: D000998:Antiviral Agents; D007211:Indoles; C086979:umifenovir; D013440:Sulfides
keywords: Arbidol; Chikungunya virus; Indoles