Nogalamycin is an
anthracycline antibiotic which was markedly cytotoxic in vitro and was active against several
tumor systems in vivo. We compare here the lethality of several
nogalamycin analogs against Chinese hamster ovary (CHO), mouse
leukemia (L1210), and mouse
melanoma (B16) cells in culture.
7-con-O-Methylnogarol (7-con-OMEN) was the most lethal of all the analogs tested. Thus, for CHO cells exposed for two hr to the
drug, the 50% lethal doses of 7-con-OMEN,
nogalamycin, and dis-nogamycin were 0.25, 2.7, and 5.8 micrograms/ml, respectively. In general, CHO cells were less sensitive than B16 or L1210 cells to most compounds. All compounds gave dose-survival curves which consisted of a shoulder region followed by a region of exponential decline in survival. The
nogalamycin analogs
nogalamycin, dis-nogamycin, 7-con-O-methylnogalarol, and 7-con-OMEN were selected for further study because of their greater lethality in vitro and antitumor activity in vivo. The lethality of these compounds was compared to that of
Adriamycin. 7-con-OMEN was more toxic to CHO cells than was
Adriamycin but was less toxic to B16 and L1210 cells. All of these compounds (except 7-con-O-methylnogalarol which was not tested) were more lethal to exponentially growing cells than to plateau-phase cells. The survival response after different periods of exposure to these drugs was compared. In order to make valid comparisons of the time-survival response to different drugs, the
drug concentrations chosen were such that they were equitoxic after a two-hr exposure. Under these conditions, the order of lethality after long-term exposure (8 hr to 24 hr) was
nogalamycin > dis-nogamycin > 7-con-OMEN,
Adriamycin > 7-con-O-methylnogalarol. With all the drugs, the rate of cell death increased with increasing
drug concentrations.