TY - JOUR T1 - ON THE CHEMOTHERAPEUTIC PROPERTIES OF THE SULFANIL ANILIDES JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 313 LP - 328 VL - 87 IS - 3 AU - L. H. SCHMIDT AU - CLARA L. SESLER Y1 - 1946/07/01 UR - http://jpet.aspetjournals.org/content/87/3/313.abstract N2 - A series of thirty-two sulfanilanilide derivatives have been examined for in vitro activities against pneumococci and Friedlander's bacilli and for their effectiveness against experimental infections with these organisms, with the following results. In vitro, nearly all of these sulfanilanilides possessed considerable activity against the pneumococci. Compounds with halogen, cyano-or notrogroupings in the 3' or 3',5' Positions were active. None fo the Sulfanilanilides possessed significant in vitro activities against the Friedlander's bacilli. None of the compounds demonstrated significant activity against experimental infections with either of the test organisms. Following a lead obtained in antimalarial investigations, a considerable number of the sulfanilanilides were studied for response to p-aminobenzoic acid. It was found that the antipneumococcal activities of numerous compounds were either not affected at all or were only partially blocked by p-aminobenzoic acid. Compounds reacting in this manner included those with 3' or 3',5'-chloro-, bromo-, trifluoromethyl-, nitro-, cyano-, or methoxy-substituents. In contrast to this, p-aminobenzoic acid uniformly blocked the activities of the sulfanilanilides against the Friedlander's bacilli. A more extensive study of in vitro and in vivo characteristics of the sulfanilani lides was carried out using, as the test drug, 3',5'-dibromosulfanilanilide, one of the most active of these compounds. The results of the in vitro studies showed that this substance possessed considerable activity against numerous strains of pneumococci, β-hemolytic streptococci and staphylococci, but had little activity against Friedlander's bacilli, Escherichia coli, Pseudomonas aeruginosa and various types of dysentery bacilli. Interestingly, the drug was equally active against sulfonamide-sensitive and resistant pneumococci and staphylococci. Furthermore, its activities against the various gram-positive cocci were not affected by p-aminobenzoic acid whereas activities against the gram-negative bacilli were uniformly blocked. The same general relationship held for antagonism of activity by the constituents of complex media or pus. The in vivo studies showed that the 3', 5'-dibromosulfanilanilide exerted little favorable effect on the course of experimental infections with β-hemolytic streptococci and none whatsoever on infections with pneumococci. The compound displayed considerable toxicity. The practical and theoretical implications of these findings have been discussed. 1946 by The American Society for Pharmacology and Experimental Therapeutics ER -