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.
Department of Pharmaceutical Sciences, Viale Benedetto XV, 3, 16132 Genova, Italy.
Mauro
M
Mazzei
Erika
E
Nieddu
Mariangela
M
Miele
Alessandro
A
Balbi
Marco
M
Ferrone
Maurizio
M
Fermeglia
Marco T
MT
Mazzei
Sabrina
S
Pricl
Paolo
P
La Colla
Fabio
F
Marongiu
Cristina
C
Ibba
Roberta
R
Loddo
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