Activity of Mannich bases of 7-hydroxycoumarin against Flaviviridae.
Some Mannich bases of 7-hydroxycoumarin (2) and their simple derivatives (3 and 4) were prepared and tested against viruses containing single-stranded, positive-sense RNA genomes (ssRNA(+)). This study was directed toward Flaviviridae and, in particular, HCV surrogate viruses (BVDV, YFV). The 7-hydroxy derivatives 2 were generally devoid of activity, but when position 7 was propylated, the resulting 7-propyloxy derivatives 3 were in some cases endowed with an interesting activity against BVDV. The formation of 7-benzoyl derivatives 4 gave compounds generally lacking in activity against Flaviviridae, whereas the appearance of activity against RSV has been observed. Also some unsymmetrical methylene derivatives 5-7 (namely coumarins bridged to chromones or indoles) were found moderately active in antiviral tests. Derivatives 3 were submitted to a molecular modeling study using DNA polymerase of HCV as a target. The good correlation between calculated molecular modeling IC(50) and experimental EC(50) indicates that DNA polymerase is potentially involved in the inhibition of surrogate HCV viruses.
Mazzei
Mauro
M
Department of Pharmaceutical Sciences, Viale Benedetto XV, 3, 16132 Genova, Italy.
Nieddu
Erika
E
Miele
Mariangela
M
Balbi
Alessandro
A
Ferrone
Marco
M
Fermeglia
Maurizio
M
Mazzei
Marco T
MT
Pricl
Sabrina
S
La Colla
Paolo
P
Marongiu
Fabio
F
Ibba
Cristina
C
Loddo
Roberta
R
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D004285:Dogs; D018067:Flaviviridae / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008352:Mannich Bases / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D013329:Structure-Activity Relationship; D014468:Umbelliferones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000378:metabolism
D000998:Antiviral Agents; D008352:Mannich Bases; D014468:Umbelliferones; D017361:Viral Nonstructural Proteins