title: Synthetic pregnenolone derivatives as antiviral agents against acyclovir-resistant isolates of Herpes Simplex Virus Type 1.
abstract: The conventional therapy for the management of Herpes Simplex Virus Type 1 (HSV-1) infections mainly comprises acyclovir (ACV) and other nucleoside analogues. A common outcome of this treatment is the emergence of resistant viral strains, principally when immunosuppressed patients are involved. Thus, the development of new antiherpetic compounds remains as a central challenge. In this work we describe the synthesis and the in vitro antiherpetic activity of a new family of steroidal compounds derived from the endogenous hormone pregnenolone. Some of these derivatives showed a remarkable inhibitory effect on HSV-1 spread both on wild type and ACV-resistant strains. The results also show that these compounds seem to interfere with the late steps of the viral cycle.
authors.affiliation: Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN) (CONICET - Facultad de Ciencias Exactas y Naturales), Universidad de Buenos Aires, Pabellón 2, Piso 4, Ciudad Universitaria, C1428EGA Buenos Aires, Argentina; Departamento de Química Orgánica and UMYMFOR (CONICET - Facultad de Ciencias Exactas y Naturales), Universidad de Buenos Aires, Pabellón 2, Piso 3, Ciudad Universitaria, C1428EGA Buenos Aires, Argentina.
authors.forename: María Eugenia
authors.initials: ME
authors.lastname: Dávola
authors.affiliation: Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN) (CONICET - Facultad de Ciencias Exactas y Naturales), Universidad de Buenos Aires, Pabellón 2, Piso 4, Ciudad Universitaria, C1428EGA Buenos Aires, Argentina.
authors.forename: Gisela I
authors.initials: GI
authors.lastname: Mazaira
authors.affiliation: Instituto de Biología y Medicina Experimental (IBYME), CONICET, Vuelta de Obligado 2490, C1428ADN Buenos Aires, Argentina; Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2, Piso 4, Ciudad Universitaria, C1428EGA Buenos Aires, Argentina.
authors.forename: Mario D
authors.initials: MD
authors.lastname: Galigniana
authors.affiliation: Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN) (CONICET - Facultad de Ciencias Exactas y Naturales), Universidad de Buenos Aires, Pabellón 2, Piso 4, Ciudad Universitaria, C1428EGA Buenos Aires, Argentina.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Alché
authors.affiliation: Departamento de Química Orgánica and UMYMFOR (CONICET - Facultad de Ciencias Exactas y Naturales), Universidad de Buenos Aires, Pabellón 2, Piso 3, Ciudad Universitaria, C1428EGA Buenos Aires, Argentina. Electronic address: jar@qo.fcen.uba.ar.
authors.forename: Javier A
authors.initials: JA
authors.lastname: Ramírez
authors.affiliation: Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN) (CONICET - Facultad de Ciencias Exactas y Naturales), Universidad de Buenos Aires, Pabellón 2, Piso 4, Ciudad Universitaria, C1428EGA Buenos Aires, Argentina.
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Barquero
mesh_terms: D000212:Acyclovir / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D055808:Drug Discovery; D024882:Drug Resistance, Viral; D006561:Herpes Simplex / Q000188:drug therapy; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000254:growth & development; D008826:Microbial Sensitivity Tests; D011284:Pregnenolone / Q000031:analogs & derivatives* / Q000494:pharmacology; D014709:Vero Cells
chemical_list: D000998:Antiviral Agents; D011284:Pregnenolone; D000212:Acyclovir
keywords: Acyclovir resistant; Antiviral; Herpes simplex type I; Non-natural side chains; Pregnenolone analogs