title: Chemical modification of the plant isoprenoid cytokinin N(6)-isopentenyladenosine yields a selective inhibitor of human enterovirus 71 replication.
abstract: In this study, we demonstrate that N(6)-isopentenyladenosine, which essentially is a plant cytokinin-like compound, exerts a potent and selective antiviral effect on the replication of human enterovirus 71 with an EC50 of 1.0 ± 0.2 μM and a selectivity index (SI) of 5.7. The synthesis of analogs with modification of the N(6)-position did not result in a lower EC50 value. However, in particular with the synthesis of N(6)-(5-hexene-2-yne-1-yl)adenosine (EC50 = 4.3 ± 1.5 μM), the selectivity index was significantly increased: because of a reduction in the adverse effect of this compound on the host cells, an SI > 101 could be calculated. With this study, we for the first time provide proof that a compound class that is based on the plant cytokinin skeleton offers an interesting starting point for the development of novel antivirals against mammalian viruses, in the present context in particular against enterovirus 71.
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Str. 32, Moscow 119991, Russian Federation.
authors.forename: Vitali I
authors.initials: VI
authors.lastname: Tararov
authors.affiliation: KU Leuven - University of Leuven, Department of Microbiology and Immunology, Laboratory for Virology and Chemotherapy, Rega Institute for Medical Research, Minderbroedersstraat 10, 3000 Leuven, Belgium.
authors.forename: Aloys
authors.initials: A
authors.lastname: Tijsma
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Str. 32, Moscow 119991, Russian Federation.
authors.forename: Svetlana V
authors.initials: SV
authors.lastname: Kolyachkina
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Str. 32, Moscow 119991, Russian Federation.
authors.forename: Vladimir E
authors.initials: VE
authors.lastname: Oslovsky
authors.affiliation: KU Leuven - University of Leuven, Department of Microbiology and Immunology, Laboratory for Virology and Chemotherapy, Rega Institute for Medical Research, Minderbroedersstraat 10, 3000 Leuven, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Neyts
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Str. 32, Moscow 119991, Russian Federation.
authors.forename: Mikhail S
authors.initials: MS
authors.lastname: Drenichev
authors.affiliation: KU Leuven - University of Leuven, Department of Microbiology and Immunology, Laboratory for Virology and Chemotherapy, Rega Institute for Medical Research, Minderbroedersstraat 10, 3000 Leuven, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Leyssen
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Str. 32, Moscow 119991, Russian Federation. Electronic address: smikh@eimb.ru.
authors.forename: Sergey N
authors.initials: SN
authors.lastname: Mikhailov
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D029821:Enterovirus A, Human / Q000187:drug effects*; D006801:Humans; D007541:Isopentenyladenosine / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D010944:Plants / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D007541:Isopentenyladenosine
keywords: Adenosine; Antiviral activity; Enterovirus 71; N(6)-derivatives; Synthesis