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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
Antiviral Chemistry and Chemotherapy
  • P. Selvam
  • N. Murugesh
  • M. Chandramohan
  • R. W. Sidwell, Utah State University
  • M. K. Wandersee
  • Donald F. Smee, Utah State University
Document Type
Article
Publisher
International Medical Press
Publication Date
1-1-2006
Disciplines
Abstract

4-[(1,2-Dihydro-2-oxo-3H-indol-3-ylidene)amino]-N-(4,6-dimethyl-2-pyrimidinyl)-benzenesulphonamide (SPIII-5H) and related compounds were tested for antiviral activity against influenza A (H1N1, H3N2, and H5N1) and B viruses in Madin Darby canine kidney (MDCK) cell culture. Among the compounds tested, SPIII-5H and four derivatives (5-chloro [SPIII-5Cl], 5-bromo [SPIII-5Br], 5-methyl [SPIII-5Me] and N-acetyl [SPIII-NA]) showed similar antiviral potencies,with only the 5-fluoro (SPIII-5F) derivative being ineffective. Fifty percent effective concentration (EC50) 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 μg/ml, to the H3N2 strain of influenza A at 13.8–26.0 μg/ml, to the H5N1 strain of influenza A at 3.1–6.3 μg/ml and to influenza B at 7.7–11.5 μg/ml. Confirmatory virus yield reduction studies against influenza A (H1N1) virus demonstrated antiviral activity (90% inhibition) at concentrations of 2–10 μg/ml. No cytotoxic effects were evident in actively growing uninfected cells or stationary monolayers at 100 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 dsorption/penetration, and no virucidal activity was evident. The basic molecule is amenable to diverse chemical modifications, which may improve water solubility and antiviral potency.

Citation Information
Selvam, P., N. Murugesh, M. Chandramohan, R.W. Sidwell, M.K. Wandersee, and D.F. Smee 2006. 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. Antiviral Chem. Chemother. 17: 269-274.