Breslow R, Jursic B, Yan Z F, Friedman E, Leng L, Ngo L, Rifkind R A, Marks P A
Department of Chemistry, Columbia University, New York, NY 10027.
Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5542-6. doi: 10.1073/pnas.88.13.5542.
Bishydroxamic acids are effective inducers of differentiation in murine erythroleukemia cells. Flexible analogs of suberic acid bisdimethylamide are approximately 100 times as active as the parent compound or hexamethylenebisacetamide. They also induce differentiation of human promyelocytic leukemia cells (HL-60) and a subclone of human colon carcinoma cells (HT-29-U4). Some rigid bishydroxamic acids with benzene rings in the spacers are even more active toward murine erythroleukemia cells but show curious biological differences. In contrast to the flexible molecules, those with benzene spacers show poor activity toward HL-60 cells; they also have different geometric requirements, and they are not additive with hexamethylenebisacetamide in their effect. It is likely that rigid bishydroxamic acids, with a benzene ring spacer, induce differentiation by a different mechanism in spite of their chemical resemblance to the flexible bisamide and bishydroxamic acid inducers.
双异羟肟酸是小鼠红白血病细胞分化的有效诱导剂。辛二酸双二甲酰胺的柔性类似物的活性约为母体化合物或六亚甲基双乙酰胺的100倍。它们还能诱导人早幼粒细胞白血病细胞（HL-60）和人结肠癌细胞亚克隆（HT-29-U4）的分化。一些在间隔基中有苯环的刚性双异羟肟酸对小鼠红白血病细胞的活性甚至更高，但表现出奇特的生物学差异。与柔性分子相比，带有苯间隔基的分子对HL-60细胞的活性较差；它们也有不同的几何要求，并且在作用上与六亚甲基双乙酰胺没有加和性。尽管带有苯环间隔基的刚性双异羟肟酸在化学结构上与柔性双酰胺和双异羟肟酸诱导剂相似，但它们可能通过不同的机制诱导分化。
