Ben A Sobin

ANTIMICROBIAL AGENTS FROM NATURAL SOURCES

As we review man’s ageless efforts to improve his environment, as well as his continuous struggle for existence, we are impressed with the tremendous developments in certain branches of science. In the beginning, it seemed only natural that man should have turned to nature to cure himself of nature’s ills, and his early searches for natural curative agents lead to the use of herbs, plant extracts, magic charms, etc. As our knowledge increased, there occurred a fusion of the sciences of general microbiology, bacteriology, and medicine, which is represented today by chemotherapy. Continuing our review for a moment, we pass from Fracastorius’s theory of contagion in the 16th century to the construction of a microscope by the Janssens at the turn of the 17th century. This was followed, some years later, by the discovery of a hitherto unseen world of microscopic creatures by the Dutch scientist, Leeuwenhoek, who utilized the much improved lenses which he made in his own laboratory. In the 19th century, the work of Schwann and, later, that of the great Louis Pasteur showed that some of these microbes were the probable cause of certain infections. Lister and Koch followed and further demonstrated the close relationship between medicine and bacteriology. In 1896, Gosio showed that a fungus, apparently a species of Penicillii, could produce a definite compound which was active i n mtro in preventing the growth of the anthrax bacillus. Some years later, pyocyanase was carefully studied by Emmerich and Low. As is well known, it is a product of Pseudomonas pyocyaneus and is highly effective in the destruction of many pathogenic bacteria. The concept of a rational approach to drug therapy was elaborated a few years later by Paul Ehrlich, who conceived the notion of starting with a toxic substance, such as arsenic, and introducing it into various organic compounds with the hope of obtainiig a structure which would produce an effective differential action on the disease-producing organisms and the tissue cells of the host. His signal success with Salvarsan may be considered as the beginning of modern chemotherapy. Unknowingly, of course, these workers were plowing the first furrows in the antibiotics’ field. In subsequent years, the heralded hopes of synthetic chemical therapy began to fade, only to be revived by the advent of the sulfa drugs and the numerous reports relating to the phenomenon of antibiosis, high-lighted by Fleming’s discovery of penicillin in 1929 and Dubos’s work with gramkidin about ten years later. The initial work of Woods and Fddes on the mechanism of action of the sulfonamides also caused widespread interest, which continues up to the present time. The developing theories of essential metabolites also have lead to continued investigation in the field of vitamins and antivitamins. The discovery of streptomycin by Waksman, in 1944, illustrated the

6-Aminopenicillanic acid in urine after oral administration of penicillins.

Summary 1) After oral and intravenous administration of Penicillin G and other known penicillins to mice, and oral administration to rats, dogs, rabbits, and man, 6-APA was detected in urine. After oral administration of penicillin to guinea pigs 6-APA was not detected in urine. 2) Tissue macerates of these animals failed to convert Penicillin G to 6-APA. 3) Probably 6-APA in urine is the result of microbial hydrolytic conversion of penicillin in the intestine and subsequent absorption and excretion.