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제목 |
The Experimental Studies on Antibacterial Spectra of Chemotherapeutic Agents against Tuberculosis and Leprosy on Various Species of Bacteria |
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저자 |
Young Ho Chang, and Joon Lew |
소속 |
Department of Microbiology, Yonsei University College of Medicine |
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년도 |
1967 |
권 |
4 |
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호 |
1 |
번호 |
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시작페이지 |
41 |
끝페이지 |
71 |
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첨부 |
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요약 |
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 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. 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
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, and Fourneau et al. and cuttle made experimental studies of the effects of
DDS on streptococcal infection in mice. Faget et al. found that Promin had antileprosy
effectiveness with less toxicity than DDS. Thereafter, various kinds of sulfone
derivatives have been introduced such as Promisole, Diasone sodium, Promacetin,
Sulfetrone and long-acting Sulfamethoxy Pyridasine (Lederkyn) and SU-1906, a
derivative of thiocarbanilide.
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 method in biological screening tests resulted in the slow and delayed
progress in the development of antileprosy chemotherapy. Under these circumstances,
Mycobacterium lepraemurium has been widely used as the model of experimental
approach. Recently, some of encouraging reports on the cultivation and on the animal
transmission of Mycobacterium leprae have been made.
Meanwhile, chemotherapy for tuberculosis has progressed rapidly since around 1930
and a number of effective antituberculosis drug has been discovered, namely,
Streptomycin, Para-aminosalicylic acid and Isonicotinic acid hydraside, a derivative of
thiosemicarbazone.
Buu-Hoi and Buu-Hoi et al. synthesized a series of thiocarbanilide derivatives which
possessed both antituberculosis and antileprosy effectiveness. Among these derivatives,
4-4'-diethosy thiocarbanilide (DETC) and 4-4'-diiso-amyloxy thiocarbanilide (DATC)
were the most effective ones and DETC is sold as a potent antituberculosis drug under
the trade name of Esoxyl in Korea.
Leprosy and tuberculosis are caused by the infections with similar acid fast bacteria,
i. E. , Mycobacterium leprae and Mycobacterium tuberculosis which share a common
ancestor in phylogenetic classification. As a matter of fact, most of antileprosy and
antituberculosis chemotherapeutics which are currently used share many characteristics
in common.
It has been speculated that compounds which have suppressive effects on mycoses
would be similarly suppressive to Mycobacterium tuberculosis and other mycobacteria
such as Mycobacterium lepraemurium and Mycobacterium leprae. Hayer and Woo et al.
Reported that antimycobacterial therapeutics had good effectiveness in treating fungal
infections, and Kim found that synthesized thiocarbanilides, L-1 and L-4, having potent
antituberculosis and antileprosy activities showed remarkable antifungal activities in in
vitro test.
So far, no comprehensive study has been made on the antibacterial spectra against
common bacteria of various antileprosy and antituberculosis chemotherapeutics which are
widely in use today.
It is hoped that this line of study might 1) prove definitely that such antileprosy and
antituberculosis chemotherapeutic agents exert specific and selective antibacterial
activities against mycobacteria and fungi, 2) reveal some of hitherto unknown
therapeutic effects possessed by them, 3) uncover the possible influences, if there any,
on normal flora of human body through the prolonged time of treatments and 4) provide
a clue in the process of developing practical test method for the screening of antileprosy
and antitubercutosis chemotherapeutics.
In conjunction with their potent antileprous and antituberculous activities and
remarkable antifungal activities of synthesized thiocarbanilides, L-1 and L-4, Oh found
that L-1 and L-4 also exhibited significant antimycobacterial activities in vitro against
the primary drug resistant strains of Mycobacterium tuberculosis. In this study,
antimycobacterial activities of L-1 and L-4 against different strains of the primary drug
resistant Mycobacterium tuberculosis were tested in order to confirm and extend Oh's
result and to provide commutative data in support of L-1 and L-4 administration to the
patients suffering from the infections with such drug resistant Mycobacterium
tuberculosis.
In an attempt of elucidating general patterns of antibacterial spectra of various kinds
of antileprosy, antituberculosis agents and synthesiged thiocarbanilides, L-1 and L-4, in
vitro studies on the antibacterial activities of antileprosy drugs (DDS, Sodium sulfoxone,
SU-1906 and Sulfamethoxy pyridazine), antituberculosis drugs (PAS, INH, SM and
DETC) and synthesized thiocarbanilides, L-1 and L-4 against a series of pathogenic and
nonpathogenic bacteria were carried out in this investigation. At the same time, tests of
antimycobacterial activities of L-1 and L-4 against the primary drug resistant strains of
Mycobacterium tuberculosis were also included in this investigation to serve as control
in testing antibacterial spectra and to confirm and extend other's result reported
previously. |
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