TUBERCULOCIDAL ACTIVITY AND TOXICITY OF SOME DIPHENYLMETHANE DERIVATIVES

¹ Research Department, Pitman-Moore Company, Division of Allied Laboratories, Inc., Indianapolis, Indiana

1. Twenty-eight derivatives of diphenylmethane have been tested for anti-bacterial activity against tubercle bacilli. Thirteen of the compounds were bactericidal at concentrations ranging from 0.063 to 4.0 mgm. per cent.

2. An attempt has been made to correlate both activity and toxicity with chemical constitution.

3. Activity, in general, appeared dependent upon halogen and hydroxy group substitution in the parent structure, and more particularly upon position.

4. Bis(2-hydroxy-5-bromophenyl)methane completely inhibited growth of tubercle bacilli at 0.25 mgm. per cent, with an LD₅₀ for mice of 2.0 gm./kgm.

The corresponding dichloro derivative was equally as active but twice as toxic. Compounds with other radicals in the 2,2'-5,5'-positions possessed only slight or no demonstrable inhibitory action, namely, 2,2'-dihydroxy-5,5'-dinitro; 2,2'-dihydroxy-5,5'-diarsono; 2,2'-dihydroxy-5,5'-di-tert.-butyl; 2,2'-dihydroxy-5,5'-di-tert.-amyl; and 2,2'-dimethyl-5,5'-di-isopropyl.

5. Bis(2-hydroxy-3,5,6-trichlorophenyl)methane was the most active of the derivatives studied, effecting complete inhibition at 0.063 mgm. per cent. It was also, however, the most toxic, LD₅₀ of 0.08 gm./kgm.