232 



THE ACTINOMYCETES, Vol. I 



Figure 88. Antifungal activity of a strepto- 

 rayces. The two filamentou.s fungi are resistant 

 and the two yeasts are sensitive. 



Katz, and Vining (1958) proposed a system 

 for classifying the various actinomycins, 

 based on their chemical structure. The paper 

 chromatographic methods are very conven- 

 ient for their differentiation. 



Among the interesting developments in 

 connection with the study of the actinomy- 

 cins is their effect upon neoplastic growths. 

 The work of Hackmann, begun in 1952, on 

 the effect of actinomycin C on experimental 

 tumors and the clinical observations of 

 Schulte and Lings (1953) opened a new field 

 for the potential utilization of this group 

 of antibiotics as chemotherapeutic agents. 

 These results were soon confirmed by a num- 

 ber of clinical investigators. It is sufficient to 

 mention the studies of Trounce et ah, Sigiura 

 and Schmidt, Nitta et al., Yamashita et al., 

 and Farber and Burchinal (1958). These 

 studies brought out the fact that although 

 (iiffei'ent actinomycins may vary somewhat 

 in their toxicity, they are similar in their 

 cytostatic activity (Pugh et al., 1956). Foley 

 reported his observations on the mechanism 

 of the action of actinomycin in bacterial 

 systems (For a review of the literature, see 



Reilly, 1953; Waksman, 1954; and Hack- 

 mann, 1955). 



The Basic Antibiotics 



Streptothricin 



The first basic antibiotic was isolated from 

 a culture of *S'. lavendulae by Waksman and 

 Woodruff in 1942. They named it strepto- 

 thricin, thus honoring F. Cohn's first desig- 

 nation of an actinomycete culttu'e. It was 

 found to possess highly desirable chemical 

 and biological propcn-ties and it offered prom- 

 ise of becoming an important chemothera- 

 peutic agent. It was water-soluble and ther- 

 mostable. It was active against various 

 gram-positive and gram-negative bacteria 

 and fungi. It was less toxic than actinomy- 

 cin, but more toxic than penicillin, an anti- 

 biotic that had come to occupy an important 

 place in chemotherapy. Its delayed toxicity 

 prevented its immediate clinical use (Waks- 

 man, 1943). 



The in vivo activity of streptothricin was 

 first established by Metzger et al. (1942); 

 its action upon the tuberculosis organism 

 was later demonstrated by Woodruff and 

 Foster (1944). It was later crystallized by 

 Fried and Wintersteiner (1945), and by 

 Kuehl et al. (1945-1946). The search for 

 streptothricin-like substances continued for 

 a long time, partly because of their anti- 

 tuberculosis properties (Weiser et al.) and 

 partly because of their intriguing chemistry. 

 Numerous related compounds were described 

 under a variety of different names. 



Numerous other preparations were later 

 isolated from cultures of *S. lavendulae (Bo- 

 honos et al.). Some were found to be the same 

 as streptothricin, and others were either 

 closely related or comprised mixtui'es of dif- 

 ferent antibiotics. 



Soon after the isolation of streptothricin, 

 another antibiotic, designated as proactino- 

 mycin, was isolated (Gardnei- and Chain, 



