Polyhydroxylated sulfated steroids derived from 5α-cholestanes as antiviral agents against herpes simplex virus.
Twelve polyhydroxylated sulfated steroids synthesized from a 5α-cholestane skeleton with different substitutions in C-2, C-3 and C-6 were evaluated for cytotoxicity and antiviral activity against herpes simplex virus (HSV) by a virus plaque reduction assay. Four compounds elicited a selective inhibitory effect against HSV. The disodium salt of 2β,3α-dihydroxy-6E-hydroximine-5α-cholestane-2,3-disulfate, named compound 7, was the most effective inhibitor of HSV-1, HSV-2 and pseudorabies virus (PrV) strains, including acyclovir-resistant variants, in human and monkey cell lines. Preliminary mechanistic studies demonstrated that compound 7 did not affect the initial steps of virus entry but inhibited a subsequent event in the infection process of HSV.
Laboratorio de Virología, Departamento de Química Biológica- IQUIBICEN (CONICET-UBA), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, Piso 4, 1428, Buenos Aires, Argentina.
Carlos A
CA
Pujol
Laboratorio de Virología, Departamento de Química Biológica- IQUIBICEN (CONICET-UBA), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, Piso 4, 1428, Buenos Aires, Argentina.
Claudia S
CS
Sepúlveda
Departamento de Química Orgánica- UMYMFOR (CONICET-UBA), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, Piso 3, 1428, Buenos Aires, Argentina.
Victoria
V
Richmond
Departamento de Química Orgánica- UMYMFOR (CONICET-UBA), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, Piso 3, 1428, Buenos Aires, Argentina.
Marta S
MS
Maier
Laboratorio de Virología, Departamento de Química Biológica- IQUIBICEN (CONICET-UBA), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, Piso 4, 1428, Buenos Aires, Argentina. edamonte@qb.fcen.uba.ar.
Elsa B
EB
Damonte
D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002776:Cholestanes / Q000737:chemistry / Q000494:pharmacology*; D006558:Herpes Genitalis / Q000821:virology; D006561:Herpes Simplex / Q000821:virology; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000502:physiology; D018258:Herpesvirus 2, Human / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D015394:Molecular Structure; D013256:Steroids / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D053586:Virus Internalization / Q000187:drug effects
D000998:Antiviral Agents; D002776:Cholestanes; D013256:Steroids
5α-Cholestanes; Antiviral activity; Herpes simplex virus; Polyhydroxylated sulfated steroids