Novel 3-sulphonamido-quinazolin-4(3H)-one derivatives: Microwave-assisted synthesis and evaluation of antiviral activities against respiratory and biodefense viruses

Abstract

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 μg/ml, CC50>100 μg/ml, SI>11.9) as did 4-(6-bromo-4oxo-2phenylquinazolin-3(4H)-yl)benzene] sulphonamide 5 (EC50=3 μg/ml, CC50= 32 μg/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. ©2007 International Medical Press.