Comparison of 4,4'-diaminodiphenylsulfone and its thymolated derivative in experimental tuberculosis in guinea pigs.

Although 4,4’-diaminodiphenylsulfone (DDS) has definite antituberculosis effects in guinea pigs infected with the human type of tubercie bacilli,’ the toxicity of this drug has precluded its acceptance in the treatment of tuberculosis in humans. DDS and a few of its derivatives are widely used in leprosy because no other equally effective agents are available for the treatment of this disease; however, the toxicity of these drugs also limits their usefulness in this disease.2 Consequently, a large number of derivatives of DDS have been prepared and studied in an effort to obtain a relatively nontoxic but active antimycobacterial drug. The evidence indicates that most of these derivatives may have no advantage over DDS itself.35 Of current interest is a derivative of DDS that is said to be relatively nontoxic. It is 4,4’-bis (6-thymylazo) -diphenylsulfone, which is derived from DDS by diazotization and coupling with thymol (Fig. 1). This drug will be referred to as DDS-thymol. Therapeutic trials with DDS-thymol in tuberculous patients who failed to respond to other treatment indicated that the drug had beneficial effects and was nontoxic.’-7 It is reported to be nontoxic for guinea pigs,8 which is in contrast to the well known hematotoxic effect in guinea pigs of DDS and some of its derivatives.5 DDS-thymol had no therapeutic activity in experimental tuberculosis in mice.’ In tuberculous guinea pigs, however, the daily administration of 400 mg. of DDS-thymol increased the survival time and promoted healing of the ulcer at the site of inoculation. Also, fewer acid-fast bacilli were present in smears of various organs in comparison to the findings in untreated animals.b0 The following report describes a study in which it was found that 2dministration of DDS-thymol to tuberculous guinea pigs resulted in regression and healing of lesions as determined by gross and histopathologic examination. This compound appeared to be less effective than DDS but it was less toxic. Methods Each of 36 mature male guinea pigs, weighing approximately 600 gm. apiece, received an intraperitoneal injection of 0.1 mg. (moist weight) of virulent human-type tubercle bacilli (H37Rv). On the 16th day after infection, six animals were killed to obtain evidence that a progressive disease had been established; these six animals were the pretreatment