Anti-Influenza Virus Activities of 4-[(1,2-dihydro-2-oxo-3H-indol-3-ylidene)amino]-N-(4,6-dimethyl-2-pyrimidin-2-yl)benzenesulphonamide and its Derivatives

Abstract

4-[(1,2-Dihydro-2-oxo-3H-indol-3-ylidene)amino]-N-(4,6-dimethyl-2-pyrimidinyl)-benzenesulphonamide (SPIII-5H) values were determined in cytopathic effect (CPE) inhibition assays quantified by neutral red dye uptake. By this method, the active compounds were inhibitory to the H1N1 strain of influenza A at 2.7-5.2 µ µg/ml, to the H3N2 strain of influenza A at 13.8-26.0 µ µg/ml, to the H5N1 strain of influenza A at 3.1-6.3 µ µg/ml and to influenza B at 7.7-11.5 µ µg/ml. Confirmatory virus yield reduction studies against influenza A (H1N1) virus demonstrated antiviral activity (90% inhibition) at concentrations of 2-10 µ µg/ml. No cytotoxic effects were evident in actively growing uninfected cells or stationary monolayers at 100 µ µg/ml. Potencies of the compounds were similar to those of ribavirin, but much less than those of oseltamivir carboxylate against the various viruses. Time-of-addition studies indicated the compounds inhibited an early step in the virus replication cycle, probably virus adsorption/penetration, and no virucidal activity was evident. The basic molecule is amenable to diverse chemical modifications, which may improve water solubility and antiviral potency.

Treatment of oseltamivir-resistant influenza A (H1N1) virus infections in mice with antiviral agents

“…Ribavirin was the least potent in cell culture of the compounds tested. The relative potencies identified for these compounds in vitro are similar to published reports for oseltamivir (Smee et al, 2001), peramivir (Smee et al, 2001), zanamivir (Smee et al, 2001), amantadine (Furuta et al, 2002), rimantadine (Valette et al, 1993), and ribavirin (Selvam et al, 2010; Selvam et al, 2006; Sleeman et al, 2010), against these or other wild-type influenza A (H1N1) virus strains. Resistance of the pandemic 2009 H1N1 viruses to adamantanes has been previously described (Gubareva et al, 2010; Mossad, 2009), and is attributable to an S31N mutation in the M2 gene.…”

Cytotoxicity study of dimethylisatin and its heterocyclic derivatives

“…But compounds containing rings far apart from the isatin ring system showed lower activity (compound 7 and 7'). Selvam et al, 2006 showed that brominated isatin derivatives had higher activity but this study showed that it was the methoxy group which showed greater activity (compound 7, LD50 36 ppm; compound 7', LD50 31 ppm and compound 8, LD50 29 ppm; compound 8', LD50 24 ppm).…”

Novel 3-sulphonamido-quinazolin-4(3H)-One Derivatives: Microwave-Assisted Synthesis and Evaluation of Antiviral Activities against Respiratory and Biodefense Viruses

“…Recently we reported the activities of certain benzenesulphonamides against influenza viruses in cell culture (Selvam et al, 2006). The potencies of some of them exceeded those of the present quinazolinone series.…”