Streeter D G, Taylor D L, Acton E M, Peters J H
Cancer Chemother Pharmacol. 1985;14(2):160-4. doi: 10.1007/BF00434357.
A series of quinone- and sugar-modified analogs of adriamycin have been tested for growth inhibition of adriamycin-sensitive (P388/S) and -resistant (P388/ADR) sublines of P388 murine leukemia cells in vitro. P388/ADR is less resistant to analogs of adriamycin containing either a 3'-deamino-3'-(4"-morpholinyl) group, MRA; or a -(3"-cyano-4"-morpholinyl) group, MRA-CN, than to adriamycin. However, MRA-CN was the most potent growth inhibitor of either subline. This potency is reduced by either modification of the quinone unit with a 5-imino substituent or restriction of the cyano-morpholinyl ring by an oxygen bridge to the daunosamine sugar. The calcium antagonist verapamil substantially increases the cytotoxicity of adriamycin to P388/ADR but has no appreciable effect on the cytotoxicity of either MRA or MRA-CN. The results suggest that increased uptake and retention by both MRA and MRA-CN may contribute to their increased cytotoxicity, but that the intense potency of the cyano-morpholinyl analogs must be due to other unique properties of these compounds.
已对一系列阿霉素的醌修饰和糖修饰类似物进行了测试，以考察其对P388小鼠白血病细胞的阿霉素敏感亚系（P388/S）和耐药亚系（P388/ADR）的体外生长抑制作用。与阿霉素相比，P388/ADR对含有3'-脱氨基-3'-(4''-吗啉基)基团（MRA）或-(3''-氰基-4''-吗啉基)基团（MRA-CN）的阿霉素类似物的耐药性较低。然而，MRA-CN是这两个亚系中最有效的生长抑制剂。用5-亚氨基取代基修饰醌单元或通过氧桥将氰基-吗啉基环与柔红糖胺糖连接起来，都会降低这种效力。钙拮抗剂维拉帕米可显著增强阿霉素对P388/ADR的细胞毒性，但对MRA或MRA-CN的细胞毒性没有明显影响。结果表明，MRA和MRA-CN摄取和潴留的增加可能有助于其细胞毒性的增强，但氰基-吗啉基类似物的强效必定归因于这些化合物的其他独特性质。
