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Title: 4''-Benzoylureido-TSAO derivatives as potent and selective non-nucleoside HCMV inhibitors. Structure-activity relationship and mechanism of antiviral action
Authors: de Castro, Sonia ×
Peromingo, M
Naesens, Lieve
Andrei, Graciela
Snoeck, Robert
Balzarini, Jan
Velázquez, Sonsoles
Camarasa, Mariá-José #
Issue Date: 25-Sep-2008
Publisher: ACS Publications
Series Title: Journal of Medicinal Chemistry vol:51 issue:18 pages:5823-5832
Abstract: Analogues of the 4''-benzoyl-ureido-TSAO derivative ( 1) modified at different positions have been prepared and evaluated against wild-type strains of HCMV and murine cytomegalovirus (MCMV) in cell culture. In addition, the activity of the most active derivatives against several drug-resistant HCMV mutants has been determined. A stringent structure-antiviral activity relationship was observed for the 4''-benzoylureido-TSAO derivatives for which the concomitant presence of a highly lipophilic substituent at both 2'- and 5'-positions was required to fully preserve the antihuman cytomegalovirus efficacy. Time-of-addition studies and HCMV immediately early and early gene expression studies revealed a target at the time of viral DNA synthesis, although direct inhibition of HCMV-encoded DNA polymerase could not be observed in cell-free assays. Lack of cross-resistance against a broad variety of mutant HCMV strains points to an antiviral target that is different from those drugs that are currently approved for clinical use.
URI: 
ISSN: 0022-2623
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
× corresponding author
# (joint) last author

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