title: New 4-Acyl-1-phenylaminocarbonyl-2-phenylpiperazine Derivatives as Potential Inhibitors of Adenovirus Infection. Synthesis, Biological Evaluation, and Structure-activity Relationships.
abstract: The search for human adenovirus (HAdV)-specific antiviral drugs for the treatment of HAdV infections in immunocompromised patients continues to be a challenging goal for medicinal chemistry. Here, we report the synthesis, biological evaluation, and structure-activity relationships of a small molecules library. We have identified six phenylpiperazine derivatives that significantly inhibited HAdV infection. These six compounds showed the capacity to block HAdV and, in addition, human cytomegalovirus (HCMV) replications at low micromolar concentration, with little or no cytotoxicity. On the basis of our biological studies, these molecules block HAdV and HCMV infections in different phases of their life cycle, providing potential candidates for the development of a new family of antiviral drugs for the treatment of infections by DNA viruses.
authors.affiliation: Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville , E41013 Seville, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Sánchez-Céspedes
authors.affiliation: Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville , E41013 Seville, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Martínez-Aguado
authors.affiliation: Department of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Seville , Profesor García González 2, E-41071 Seville, Spain.
authors.forename: Margarita
authors.initials: M
authors.lastname: Vega-Holm
authors.affiliation: Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville , E41013 Seville, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Serna-Gallego
authors.affiliation: Department of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Seville , Profesor García González 2, E-41071 Seville, Spain.
authors.forename: José Ignacio
authors.initials: JI
authors.lastname: Candela
authors.affiliation: Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville , E41013 Seville, Spain.
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Marrugal-Lorenzo
authors.affiliation: Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville , E41013 Seville, Spain.|Department of Medicine, University of Seville , E-41009 Seville, Spain.
authors.forename: Jerónimo
authors.initials: J
authors.lastname: Pachón
authors.affiliation: Department of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Seville , Profesor García González 2, E-41071 Seville, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Iglesias-Guerra
authors.affiliation: Department of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Seville , Profesor García González 2, E-41071 Seville, Spain.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Vega-Pérez
mesh_terms: D000258:Adenovirus Infections, Human / Q000188:drug therapy*; D000260:Adenoviruses, Human / Q000187:drug effects*; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents