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INHIBITION OF BACTERIA BY 5-FLUORONICOTINIC ACID AND OTHER ANALOGUES OF NICOTINIC ACID

The Lilly Research Laboratories, Indianapolis, Indiana

ABSTRACT

STREIGHTOFF, FRANK (The Lilly Research Laboratories, Indianapolis, Ind.). Inhibition of bacteria by 5-fluoronicotinic acid and other analogues of nicotinic acid. J. Bacteriol. 85:42–48. 1963.—Several compounds related to 5-fluoronicotinic acid (5-FNA) have been demonstrated to inhibit Streptococcus sp. (Viridans group), Staphylococcus aureus, Escherichia coli, and Lactobacillus plantarum in vitro. The most active compounds were 5-FNA and 5-fluoronicotinamide (5-FNAM). The growth of Streptococcus sp. was inhibited more than 50% by 0.05 µg/ml of 5-FNA or 0.5 µg/ml of 5-FNAM. The inhibition of Streptococcus sp. from 1 part of 5-FNA or 5-FNAM was reversed by 4 and 2 parts of nicotinic acid, respectively. The inhibition of E. coli from 100 parts of 5-FNA or 5-FNAM was reversed by 1 part of nicotinic acid. Inhibitions by most other active compounds could be reversed by nicotinic acid. In experiments with mice, eight compounds related to 5-FNA had activity against Streptococcus pyogenes; 5-FNA, 5-FNAM, and 5-fluoro-N-dimethylaminomethylnicotinamide protected all mice at 83 mg/kg x two treatments subcutaneously. The action of 200 mg/kg x two treatments of 5-FNA was reversed by 20 mg/kg x two treatments of nicotinic acid. The activity of 5-FNA was not increased by modifications at the number 3 or 5 positions on the pyridine ring or by any other structural changes.