Novel 3-sulphonamido-quinazolin-4(3H)-one derivatives: microwave-assisted synthesis and evaluation of antiviral activities against respiratory and biodefense viruses.
We designed and synthesized novel 2,3-disubstituted quinazolin-4(3H)-ones by microwave technique and characterized them by spectral analysis. Synthesized compounds were screened for cytotoxicity and for antiviral activity against influenza A (H1N1, H3N2 and H5N1), severe acute respiratory syndrome corona, dengue, yellow fever, Venezuelan equine encephalitis (VEE), Rift Valley fever, and Tacaribe viruses in cell culture. A neutral red uptake assay was used to determine 50% virus-inhibitory concentrations (EC50) of test compounds and their 50% cytotoxicity concentration (CC50) in uninfected Madin-Darby canine kidney, Vero, and Vero 76 cells; selectivity indices (ratio of CC50 to EC50) were derived from the data. The compound 4-(6,8-dibromo-4-oxo-2-phenyl quinazolin-3(4H)-yl)-N-(4,5-dimethyloxazol-2yl) benzenesulphonamide 15 inhibited the replication of avian influenza (H5N1) virus (EC50 = 8.4 microg/ml, CC50 > 100 microg/ml, SI > 11.9) as did 4-(6-bromo-4oxo-2phenylquinazolin-3(4H)-yl) benzene]sulphonamide 5 (EC50 = 3 microg/ml, CC50 = 32 microg/ml, SI = 11). Compound 5 was also moderately active against VEE and Tacaribe viruses. The methodology described in this report is applicable for rapid synthesis of many compounds with potential antiviral properties.
Selvam
Periyasamy
P
Arulmigu Kalasalingam College of Pharmacy, Krishnankoil-626190, India. periyasamyselvam2001@yahoo.co.in
Vijayalakshimi
Paulchamy
P
Smee
Donald F
DF
Gowen
Brian B
BB
Julander
Justin G
JG
Day
Craig W
CW
Barnard
Dale L
DL
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000528:radiation effects; D002522:Chlorocebus aethiops; D004285:Dogs; D008826:Microbial Sensitivity Tests; D008872:Microwaves; D015394:Molecular Structure; D052999:Quinazolinones / Q000138:chemical synthesis / Q000494:pharmacology* / Q000528:radiation effects; D013449:Sulfonamides / Q000138:chemical synthesis / Q000494:pharmacology* / Q000528:radiation effects; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects; D014780:Viruses / Q000187:drug effects*
D000998:Antiviral Agents; D052999:Quinazolinones; D013449:Sulfonamides