A New Glass of Tuberculostatic Substances

Abstract

The search for substances having tuberculostatic activity has in recent years engaged increasing interest in many laboratories. Using an in vitro technic in which a rapidly growing avirulent strain of “human” tuberculosis organism is subjected to various concentrations of compounds under test makes feasible the “screening” of large numbers of substances in a comparatively short time. This method, the details of which are essentially the same as described earlier 1 has brought to attention 5-amino-2-butoxypyridine which was investigated in some detail. Several hundred derivatives of this substance were synthesized† one of which, the sodium formaldehyde bisulfite derivative relatively among the least toxic, 2 is included in this report.

The growth of 607, the rapidly growing strain of the tubercle bacillus, was inhibited by these compounds in dilutions in excess of 1 to 3 million. Other strains, virulent and recent isolations, were inhibited in dilutions as high as 1 to 100 million. A remarkable feature associated with this high tuberculostatic effect is that while several bacterial genera have been investigated only Mycobacterium was susceptible to the action of these substances in significant dilution. The data presented in Table I are typical of the results obtained in many-time repeated experiments. The specificity for Mycobacterium is illustrated by the lack of inhibition of growth of Staphylococcus, Streptococcus, Pneumococ-cus, B. mycoides, E. colt, and others, even in what may be termed high concentrations. This specificity contrasts sharply with the lack of specificity shown by sulfones and sulfonamides 1 which are active against the rapidly growing avirulent Mycobacterium tuberculosis 607 (line No. 1) as well as E. coli in a synthetic medium (line No. 10). Comparison is also made with promin and its parent substance p, p'-diaminodiphenylsulfone.

It is important also to note that while the more active sulfonamide and sulfones are capable of inhibiting the growth of the avirulent strain of tubercle bacillus in comparatively high dilution (line No. 1), these compounds are relatively ineffective against other more virulent strains (lines 2, 3 and 4).