Dimmock J R, Chamankhah M, Seniuk A, Allen T M, Kao G Y, Halleran S
College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Canada.
Pharmazie. 1995 Oct;50(10):668-71.
A number of Mannich bases of alicyclic ketones containing one and two basic centres were prepared in order to evaluate the theory of sequential cytotoxicity and develop structure-activity relationships in these series of compounds. The compounds were evaluated in vitro against murine P388 D1 lymphocytic leukemia cells. The data generated supported the theory of sequential cytotoxicity and in general, compounds containing alicyclic rings of five and six carbon atoms possessed greater activity than the corresponding dodecyl analogues. Those Mannich bases containing dialkylamino groups were associated with greater cytotoxicity than related compounds possessing a basic heterocycle. Calculations of the atomic charges of the enone groups from selected compounds afforded some rationalization for the cytotoxic screening results.
制备了一系列含有一个和两个碱性中心的脂环族酮曼尼希碱，以评估序贯细胞毒性理论，并建立这些系列化合物的构效关系。在体外对这些化合物针对小鼠P388 D1淋巴细胞白血病细胞进行了评估。所产生的数据支持序贯细胞毒性理论，并且一般来说，含有五和六个碳原子脂环的化合物比相应的十二烷基类似物具有更高的活性。那些含有二烷基氨基的曼尼希碱比具有碱性杂环的相关化合物具有更高的细胞毒性。对所选化合物烯酮基团的原子电荷计算为细胞毒性筛选结果提供了一些合理的解释。
