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.
Arulmigu Kalasalingam College of Pharmacy, Krishnankoil-626190, India. periyasamyselvam2001@yahoo.co.in
Periyasamy
P
Selvam
Paulchamy
P
Vijayalakshimi
Donald F
DF
Smee
Brian B
BB
Gowen
Justin G
JG
Julander
Craig W
CW
Day
Dale L
DL
Barnard
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