Limitless numbers of various genetic structures have been formed in chromosomes and plasmids and numerous bioactive compounds are produced by microorganisms. Therefore, it may be said that compounds useful in treatment of
cancer will be found more and more in microbial secondary metabolites and more effective antitumor
antibiotics and their derivatives, or more effective products producing immune resistance to
cancer, will be discovered. In these studies, as discussed in this paper, the most urgent problem is to establish a rational screening principle or system to select compounds worth clinical examination. This is particularly important in the analog area.
Bleomycin is an analog of
phleomycin chosen because of lower renal toxicity. It has become an
antitumor agent of significant value. Macromycin is a new structure which has been found to bind with animal cells and inhibit growth. Neothramycin is a new
benzodiazepine antibiotic which has lower toxicity than other structures studied in this class and is active against L1210,
Yoshida sarcoma, and
Sarcoma 180.
Aclacinomycin A is an analog of
adriamycin chosen for clinical study based on its low
cardiac toxicity and high distribution in mouse lung and spleen. Coriolins are another new structural class.
Diketocoriolin B has activity in
L1210 leukemia and has been shown to inhibit Na-K-
ATPase.
Bestatin is a compound which inhibits
aminopeptidase B and
leucine aminopeptidase has been shown to increase
delayed hypersensitivity.
Bestatin also increases the effects of other
antitumor agents such as
adriamycin, and
bleomycin.