Synthesis and biological evaluation of dihydrofuran-fused perhydrophenanthrenes as a new anti-influenza agent having novel structural characteristic.
Dihydrofuran-fused perhydrophenanthrenes were synthesized by means of o-quinodimethane chemistry with high generality and stereoselectivity, and found to exhibit potent anti-influenza activity. These compounds exerted an inhibitory effect on various strains of influenza virus growth, including influenza A and B, with a concentration dependent manner, and direct cytotoxicity was low. Several biological experiments suggested that these new drugs affected a virus replication process before mRNA synthesis stage. Novel rigid cage-type of structural characteristic of the compounds has not been found in hitherto anti-influenza drugs, and will provide new basis and motif for exploring promising and unprecedented anti-influenza agents.
Matsuya
Yuji
Y
Faculty of Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Sasaki
Kazushige
K
Ochiai
Hiroshi
H
Nemoto
Hideo
H
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D005663:Furans / Q000737:chemistry*; D009980:Influenza A virus / Q000187:drug effects* / Q000254:growth & development; D009981:Influenza B virus / Q000187:drug effects* / Q000254:growth & development; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D010616:Phenanthrenes / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D005663:Furans; D010616:Phenanthrenes