Studies on Highly Soluble Azo Sulfonamides.

Since the early observations of Kellner (1936) and Fuller (1937), who demonstrated that p-aminobenzenesulfonamide (sulfanilamide) is formed in animal tissues when prontosill or prontosil soluble2 (neoprontosil3) is administered by mouth, and the studies by Domagk (1935), Colebrook and Kenney (1936), and Colebrook, Buttle, and O'Meara (1936), wherein they were unable to demonstrate an antibacterial effect on the part of the latter compounds in titro, very little attention has been directed to similar studies on other azo sulfonamides. Inasmuch as several heterocyclic substituted sulfanilamide derivatives, namely, sulfathiazole, sulfapyridine, and sulfadiazine, have proved to be superior to sulfanilamide in their antibacterial effects against many organisms both in vitro and in vivo, it appeared worth while to compare the activity of these compounds with that of their azo sulfonamide counterparts. An azo preparation with interesting properties, including the ability to inactivate lysozyme (Lawrence and Klingel, 1943), was prepared by coupling diazotized sulfathiazole with the symmetrical carbamide of 2R acid. The other soluble azo dyes were formed by coupling the diazotized parent sulfonamide compounds with sodium 1-hydroxy-7-acetylaminonaphthalene-3,6-disulfonate, hereafter described as "acetyl-2R acid." Diphenyl-sulfone-4,4'-disazo-acetyl2R acid (a sulfone) and 6-sulfaquinoline-azo-acetyl-2R acid completed the series of drugs studied. The structural formulae and molecular weights of several of these compounds are given in figure 1. The organisms against which the compounds were tested in vitro included Staphylococcus aureus 209, Streptococcus pyogenes C-203, a viridans streptococcus, types I, II, and III pneumococci, and members of the Brucella group.