Novel anti-respiratory syncytial(RS) viral compounds: benzodithiin derivatives.
Benzodithiin derivatives are highly potent and specific inhibitors of respiratory syncytial virus (RSV) replication in vitro. The most potent and selective congener of a benzodithiin derivative is 1,4-dihydro-2,3-benzodithiin(RD3-0028). According to the modified 3-(4,5-dimethylthiazole-2-yl) 2,5-diphenyl tetrazolium bromide (MTT) assay developed in our laboratories, this compound has a 50% effective concentration of 4.5 microM and a 50% cytotoxic concentration of 271.0 microM, which is superior to that of ribavirin. This compound also inhibits RSV strain subgroups A and B and clinical isolates. RD3-0028, however, does not inhibit the replication of influenza A virus, measles virus, herpes simplex virus types 1 and 2, or human cytomegalovirus. Two other benzodithiin derivatives [1,4-dihydro-6-methyl-2,3-benzodithiin (RD3-0270) and 1,4-dihydro-5-methyl-1-2,3-benzodithiin (RD3-0284)] also inhibit RSV replication at a selectivity index greater a factor of 20. These results suggest that the benzodithiin skeleton is an important structure for inhibitory activity against RSV replication.
Watanabe
W
W
Rational Drug Design Laboratories, Fukushima, Japan.
Sudo
K
K
Sata
R
R
Kajiyashiki
T
T
Konno
K
K
Shigeta
S
S
Yokota
T
T
D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D006367:HeLa Cells; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D018113:Respiratory Syncytial Virus, Human / Q000145:classification / Q000187:drug effects* / Q000502:physiology; D012254:Ribavirin / Q000494:pharmacology; D013778:Tetrazolium Salts; D013844:Thiazoles; D013997:Time Factors; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D006571:Heterocyclic Compounds; D013778:Tetrazolium Salts; D013844:Thiazoles; D012254:Ribavirin; C022616:thiazolyl blue