Lethality of nogalamycin, nogalamycin analogs, and adriamycin to cells in different cell cycle phases.

The drugs studied included nogalamycin and its derivative 7-con-O-methylnogalarol, dis-nogamycin and its derivative 7-con-O-methylnogarol, and Adriamycin. All of these drugs, especially at high doses, were lethal to cells in every phase of the cell cycle, indicating that they were not phase specific. However, there were significant differences in drug sensitivity of cells in different parts of the cell cycle. Nogalamycin and Adriamycin were most lethal to the cells in S phase, whereas cells in M, G1, and G2 were much less sensitive. In contrast, the nogalamycin derivative 7-con-O-methylnogalarol was almost equally lethal to cells in all phases of the cell cycle. dis-nogamycin was most lethal to cells in postmetaphase and in early S phase. Cells in mid- and late G1, late S, and G2 were much less sensitive. The pattern of sensitivity to 7-con-O-methylnogarol was different from that of dis-nogamycin. 7-con-O-Methylnogarol was most lethal to cells in early G1, S, and G2. Only cells in mid- and late G1 were much less sensitive to this drug.