Antiviral activity of sodium 5-aminosulfonyl-2,4-dichlorobenzoate (M12325)

Abstract

Sodium 5-aminosulfonyl-2,4-dichlorobenzoate (M12325) was evaluated for antiviral activity in tissue culture and infected mice. At concentrations ranging from 2.5 to 75.8 micrograms/ml, M12325 inhibited the cytopathic effects of 10 mean tissue culture infective doses of influenza virus A/WSN, A/FM, A/Kumamoto, and B/Great Lakes; parainfluenza virus; rhinovirus; echovirus; respiratory syncytial virus; and vesicular stomatitis virus. Concentrations up to 150 micrograms/ml did not inhibit the cytopathic effects of herpes simplex virus, vaccinia virus, or adenovirus. Concentrations up to 3,160 micrograms/ml did not inhibit the growth of MDCK, Vero, or HEL cells in culture. Single oral doses of M12325, ranging from 10 to 300 mg/kg, administered 1 h before and 1 h after challenge, reduced mortality in mice inoculated intranasally with influenza A/WSN virus. Twice daily oral doses for 14 days effected significant reductions in the mortality of mice infected intranasally with influenza A/WSN, A/FM, A/Kumamoto, and B/Great Lakes, and parainfluenza virus, but they were not effective in mice infected with herpes simplex virus. Multiple doses of 10 and 30 mg/kg, administered intraperitoneally, reduced lung consolidation and virus titer. M12325 was well tolerated in multiple doses up to 1 g/kg orally. These observations support the conclusions that M12325 has a broad spectrum of activity against RNA viruses in vitro and in vivo, selective toxicity, and a large margin of safety.

Hypoxia-selective antitumor agents. 3. Relationships between structure and cytotoxicity against cultured tumor cells for substituted N,N-bis(2-chloroethyl)anilines

“…(2) The DNA repair cross-link defective mutant shows hypersensitivity to the nitroaniline mustards but not to the diols or other simple nitrobenzenoid compounds. (3) Their cytotoxicities are similar to those predicted for aniline mustards with strongly electron-withdrawing functionality.…”

“…The solution was washed with saturated aqueous NaHC03 and worked up to give an oil, which was chromatographed on Si02. Elution with EtOAc/petroleum ether (1:5) gave !V,lV-bis(2-chloroethyl)-3-nitroaniline (9), which was crystallized from absolute EtOH as orange plates (1.46 g, 71%); mp [110][111] °C; lH NMR (CDC13) 7.73-6.80 (m, 4 H, ArH), 3.78 (br t, 8 H, CH2N and CH2C1). See Table V for analysis.…”

Existing antivirals are effective against influenza viruses with genes from the 1918 pandemic virus

“…Amantadine hydrochloride and rimantadine hydrochloride were obtained from Sigma-Aldrich. Sensitivity of recombinant influenza viruses in tissue culture to amantadine or rimantadine was assessed with a plaque-reduction assay with modifications of methods described previously (29,30). Virus stocks used for plaque-inhibition assays were grown and titrated on MDCK cell monolayers.…”

Antirhinovirus activity of purine nucleoside analogs

“…The search for effective antirhinovirus agents has yielded a wealth of compounds belonging to widely varying chemical classes: thiosemicarbazones (20), isoquinolines (35,43), triazinoindoles (27), guanidines (5), benzoates (30), furanyls (2), benzimidazoles (12), thiourea (18), diketones (14,16,17), flavans (3,32), flavones (25), chalcones (24), nitrobenzenes (34,41), and isoxazoles (15,31). The most recently developed antirhinovirus compounds (3,15,24,31) reach their MICs within the range of 0.001 to 0.01 ,ug/ml.…”