INTRODUCTION
Progress in chemotherapy is intimately associated with the development of new screening methods; as a matter of fact, each of the great drug discoveries has been preceded and made possible by the introduction of a new and specific biological test method.
Early in 1911, Ehrlich opened the way of biological test by developing Arsphenamine through the experiment in mice affected with trypanosomiasis and Domagk (1935) successfully discovered Prontosil (2-4-diamino-azobenzene 4-sulfonamide hydrochloride) through the screening test of antibacterial agents in mice. The systematic screening method for antituberculosis agents was developed by the work of Donovick et al. (1940) who had originated a simple and easy mouse test.
Today, a number of infectious diseases, still lack adequate chemotherapy, in most instance only because we do not have at hand appropriate screening methods that duplicate, in laboratory animals, the essential biological features of these diseases. Among major infectious diseases which are still without adequate chemotherapy, are virtually all those of virus etiology, certain form of trypanosomiasis and among the bacterial diseases, in particular, leprosy and some of mycotic infections.
Hansen´s bacilli, Mycobacterium leprae, was the first pathogenic microorganism that was found to cause disease in human host. From the ancient times, Chaulmoogral oil (Mouat; 1854) has been empirically used in the treatment of leprosy. However, the initiation of modern chemotherapy for leprosy was begun by the introduction of DDS (4-4´-diaminodiphenyl sulfone) and Promin into clinical uses. DDS was originally synthesized by Fromm and Wittmann (1908), and Fourneau et al. (1937) and Buttle (1952) made experimental studies of the effects of DDS on streptococcal infection in mice. Faget et al. (1943) found that Promin had antileprosy effectiveness with less toxicity than DDS. Thereafter, various kinds of sulfone derivatives have been introduced such as Promizole, Diasone sodium, Promacetin, Sulfetrone and long-acting Sulfamethoxy pyridazine (Lederkyn) and SU-1906, a derivative of thiocarbanilide (Mayer, 1941, 1954; Mayer et al., 1953, 1959).
At present, DDS is considered the first choice of drug in the treatment of leprosy even though some of the derivatives mentioned above have been proved to be more effective and less toxic than DDS. However, DDS can never be a sole and ideal antileprosy remedy because of the facts that it is quite toxic and requires a prolonged time of administration in order to accomplish the therapeutic effect.
The development of new antileprosy chemotherapeutics had been hampered by failures of cultivation and of animal transmission of Mycobacterium leprae. Lack of more simple and reliable antituberculous and antileprous chemotherapeutics.
In this study Oh´s data (1966) was also confirmed and extended that synthesized thiocarbanilides L-1 and L-4 exhibited potent antimycobacterial activities against the primary drug resistant Mycobacterium tuberculosis. As Buu-Hoi et al. (1957) and Oh (1966) pointed out, superior antimycobacterial activities of L-1 than L-4 appears to be related with the presence of p-rhodan radical in the chemical structure of L-1.
On the basis of data shown in this study and in Oh´s (1966), the possibility of successful human trial of L-1 and L-4 in the patients suffering from infections with the primary drug resistant Mycobacterium tuberculosis became apparent. However, it should be emphasized, in advance to human trial of L-1 and L-4, the possible occurrence of L-1 or L-4 resistance in Mycobacterium tuberculosis should be determined through in vitro and in vivo animal experiments.
CONCLUSION
In vitro studies were carried out on the antibacterial spectra of currently used antileprous, antituberculous chemotherapeutics and synthesized thiocarbanilides, L-1 and L-4, against 24 strains of Gram-positive and -negative pathogenic and nonpathogenic bacteria. Tests of antimycobacterial activities of L-1 and L-4 against 10 strains of the primary drug resistant Mycobacterium tuberculosis were also included in this investigation to serve as control in testing antibacterial spectra and to confirm and extend other´s results reported previously.
1. Antibacterial spectra against common bacteria of antileprous chemotherapeutics, DDS, Sodium sulfoxone, Sulfamethoxy pyridazine and SU 1906, were nonspecific and insignificant, so that. it was impossible to establish characteristic general patterns in their antibacterial activities. These drugs, in general, possessed superior antibacterial action against pathogenic bacteria than against nonpathogenic ones. SU 1906 exhibited more or less selective antibacterial activity only against Gram-positive bacteria.
2. Antituberculous agents, PAS, INH and DETC also.exerted weak and nonspecific antibacterial actions against common bacteria, and, therefore, the establishment of characteristic general patterns in their antibacterial activities was impossible. However, Streptomycin showed the most superior and the broadest antibacterial activities among the drugs tested in this study. INH and SM possessed similar antimycobacterial activities against Mycobacterium phlei at the concentration
of 100,ug per ml.
3. Antibacterial activities against common bacteria of synthesized thiocarbanilides L-1 and L-4 were also nonspecific and insignificant, and these thiocarbanilides did not possess superior antibacterial actions against common bacteria than those of antileprous or antituberculoue chemotherapeutics tested. In general, L-1 appeared to be superior in its antibacterial activity -than L-4 and it was alike that of DETC.
Whereas, it was confirmed and extended that both L-1 and L-4 were potent antimycobacterial agents against the primary drug resistant strains of Mycobacterium tuberculosis.
4. Based on the data of nonspecific and insignificant antibacterial activities against common bacteria of antileprous and antituberculous agents and synthesized thiocarbanilides L-1 and L-4, it could be concluded that potent antileprous, antituberculous and antifungal activities possessed by such drugs are specific and selective ones.
5. It became evident that the therapeutic administration of antileprous and antituberculous chemotherapeutics and synthesized thiocarbanilides L-1 and L-4 could hardly provoke any harmful effects on normal flora of human body through the prolonged time of administration for therapeutic purposes.
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