Chemotherapy of murine leprosy. VI. The effects of isonicotinylhydrazone of 2-carboxymethoxy-3-methoxybenzaldehyde (compound 373) and isonicotinylhydrazone of 2-carboxymethoxybenzaldehyde (compound 377) on mouse leprosy.

Since the discovery of the antituberculous activity of isonicotinic acid hydrazide (isoniazid), many related chemical compounds have been studied in the hope of finding compounds still more potent, less toxic, and of longer-lasting activity. Isonicotinylhydrazones of substituted benzaldehydes have been studied by several groups of investigators. A total of 25 derivatives have been reported to be effective in experimental tuberculosis of mice, rabbits and guinea-pigs (1, 2, 10, 14, 18, 22, 23, 24, 25, 26, 28). Two were reported effective also in human tuberculosis (11, 16, 20) and one in leprosy (13). The chemical structures of these compounds and the animals in which they have been found effective are shown in Table 1. Several of these substances have been claimed to be more effective and less toxic than the parent compound, isoniazid, in experimental tuberculosis (10,23,24), and one is said to have produced better results in the treatment of leprosy (13). Siebenmann and Zubrys (26) have reported that, in mouse tuberculosis, isonicotinylhydrazone of 2-carboxymethoxybenzaldehyde (Compound 377) was more effective than isoniazid when the treatment was started immediately following the inoculation, but less active when the treatment was given seven days later; its toxicity in mice was less than one twenty-fifth of that of isoniazid. A related derivative, isonicotinylhydrazone of 2-carboxymethoxy-3-methoxybenzaldehyde (Compound 373), approached isoniazid in its in vivo antituberculosis activity, while its toxicity was less than one-fortieth of that of isoniazid. Compound 373 also revealed low toxicity in human beings, and a clinical trial in tuberculosis is in progress (27). The suppressive activity of isoniazid in murine leprosy has been reported by me and other investigators (3,5,6,8,9,12,15,21). No report on the effects of isonicotinylhydrazones of substituted benzaldehydes has been made. On account of the high activity and low toxicity of Compound 373 and Compound 377 in experimental tuberculosis, studies of their effects on mouse leprosy were undertaken. By employing equimolar doses, the