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

• Published in: Antiviral chemistry & chemotherapy 2006-10, Vol.17 (5), p.269-274
• Main Authors: Selvam, Periyasamy, Murugesh, Narayanan, Chandramohan, Markandavel, Sidwell, Robert W, Wandersee, Miles K, Smee, Donald F
• Format: Article
• Language: English
• Subjects: Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral activity; Antiviral agents; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Avian flu; Biological and medical sciences; Cell culture; Cells, Cultured; Cytotoxicity; Dogs; Human viral diseases; Indoles - chemistry; Indoles - pharmacology; Infectious diseases; Influenza A; Influenza A virus - drug effects; Influenza B; Influenza B virus - drug effects; Isatin - analogs & derivatives; Isatin - chemistry; Isatin - pharmacology; Medical sciences; Microbial Sensitivity Tests; Molecular Structure; Oseltamivir; Pharmacology. Drug treatments; Ribavirin; Structure-Activity Relationship; Sulfonamides - chemistry; Sulfonamides - pharmacology; Viral diseases; Viral diseases of the respiratory system and ent viral diseases; Virus Replication - drug effects; Viruses
• ISSN: 2040-2066; 0956-3202; 2040-2066
• DOI: 10.1177/095632020601700504

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 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.