As part of a proposed research program concerned with the biological screening of various organic compounds and directed primarily toward a search for anti-tumor agents, an investigation of the possible effects of a series of substituted pyridines on the growth of Lactobacillus casei has been initiated. Although the first phase of this work is mainly concerned with a search for compounds which possess general inhibitory properties, use has been made of several well-defined growth media devised by Hitchings et a! (1) for the study of antagonistic as well as simulatory activities with respect to the folic acid, thymine, and purine requirements of this organism. These authors have emphasized the possible relationships which such activities may bear to the biosynthesis of nucleic acids.
The observations which form the basis of this report demonstrate an appreciable inhibitory activity toward L. casei for several of the compounds studied. Little if any indication of a relationship between this activity and the nutrilites discussed above was noted.
Except for several modifications, the experimental procedure was that described by Hitchings et al (1). The composition of the basal medium (O) was modified by the use of Vitamin-Free Enzymatic Casein Hydrolysate (Nutritional Biochemicals Corp.) at a concentration corresponding to 5 g. solid per liter. Supplemen}ation of this medium with adenine sulfate (10 mg. per I.), thymine (1 mg. per 1.), or folic acid (0.05 ug. per 1.) gave media (P), (OT), and (OFA), respectively. Addition of thymine (1 mg. per 1.) to (P) and of adenine sulfate (10 mg. per 1.) to (OFA) resulted in the media (PT) and (PFA), respectively.
The extent of growth of L. casei, ATCC 9595, was determined by averaging duplicate alkali (N/10 NaOH) titration values for the lactic acid formed in 10 ml. of medium after 41-hr. growth at 37 ยฐ C. Average control growth values in terms of N/10 lactic acid produced per 10 ml. medium for the media (O), (OT), (P), (OFA), (PT), and (PFA) were 0.4, 0.5, 0.8, 3.9, 3.1, and 7.2 ml., respectively.
Each compound listed in Table I was tested in each of the six media at a concentration of 100 #g. per ml. In addition, I, II, and III were tested at 10 ug. and 1 ug. per ml.