title: Design, synthesis, and preliminary in vitro and in silico antiviral activity of [4,7]phenantrolines and 1-oxo-1,4-dihydro-[4,7]phenantrolines against single-stranded positive-sense RNA genome viruses.
abstract: Following the antiviral screening of a wide series of new angular and linear N-tricyclic systems both in silico and in vitro, the [4,7]phenantroline nucleus emerged as a new ring system endowed with activity against viruses containing single-stranded, positive-sense RNA genomes (ssRNA+). Here, we report our new pathway to the synthesis of this nucleus and of several related derivatives, as well as the results of both cell-based antiviral assays and molecular dynamics simulations. In the antiviral screening, several compounds (9 and 16-20) showed to be fairly active against BVDV, CVB-2, and Polio 1 (EC50, 6-25 microM). According to molecular dynamics simulations, compounds (15) and (17) emerged for its potency against the HCV NS5B, with a calculated IC50 of 11-12 microM.
authors.affiliation: Dipartimento Farmaco Chimico Tossicologico, Università degli Studi di Sassari, Via Muroni 23/a, 07100 Sassari, Italy. acarta@uniss.it
authors.forename: Antonio
authors.initials: A
authors.lastname: Carta
authors.forename: Mario
authors.initials: M
authors.lastname: Loriga
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Paglietti
authors.forename: Marco
authors.initials: M
authors.lastname: Ferrone
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fermeglia
authors.forename: Sabrina
authors.initials: S
authors.lastname: Pricl
authors.forename: Tiziana
authors.initials: T
authors.lastname: Sanna
authors.forename: Cristina
authors.initials: C
authors.lastname: Ibba
authors.forename: Paolo
authors.initials: P
authors.lastname: La Colla
authors.forename: Roberta
authors.initials: R
authors.lastname: Loddo
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D010618:Phenanthrolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D012328:RNA Viruses / Q000187:drug effects*; D013057:Spectrum Analysis
chemical_list: D000998:Antiviral Agents; D010618:Phenanthrolines