The Effects of Paba Derivatives on the Multiplication of Typhus Rickettsiae

The rickettsiostatic activity of 1) isosteres of PABA, 2) p-halobenzoic acids, 3) p-alkoxybenzoic acids and 4) compounds with substitutions in the carboxyl group of PABA were determined. The compounds were titrated to an upper limit which was toxic to the embryo or inhibitory to the growth of rickettsiae and to a lower limit which was non-inhibitory to the growth of rick-ettsiae. PABA and its isosteres showed the following order of activity: p-aminobenzoic acid τ; p-methylbenzoic acid τ; p-fluorobenzoic acid. p-Hydroxybenzoic acid did not exhibit rickettsiostatic activity. The order of rickettsiostatic activity of the p-halobenzoic acids was: p-iodobenzoic acid τ; p-bromobenzoic acid τ; p-chlorobenzoic acid τ; p-fluorobenzoic acid. The rickettsiostatic activity of the effective p-alkoxybenzoic acids increased directly as the length of the carbon chain: p-pentoxy benzoic acid τ; p-propoxybenzoic acid τ; p-ethoxybenzoic acid τ; p-methoxybenzoic acid. p-Butoxy-benzoic acid was not active. p-Aminohippuric acid partially inhibited the growth of rickettsiae. Other compounds containing carboxyl group substitutions (p-aminoacetophenone and p-aminopropiophenone, and methyl-p-aminobenzoate) were very toxic to the embryos and did not inhibit rickettsiostatic activity when given in tolerated doses.