Vogler W R, Olson A C, Hajdu J, Shoji M, Raynor R, Kuo J F
Department of Medicine, Emory University, Atlanta, Georgia 30322.
Lipids. 1993 Jun;28(6):511-6. doi: 10.1007/BF02536082.
This investigation was initiated in order to delineate the structure-function relationship of the anticancer alkyl-lysophospholipids and assess their degree of selective cytotoxicity toward neoplastic cells. A series of glycerol phosphocholine analogs with varying substitutions in the sn-1 and sn-2 position were tested for their inhibitory activity as measured by thymidine incorporation, clonogenic assays and effects on protein kinase C activity against a series of human leukemic cell lines and healthy bone marrow progenitor cells. The IC50 was determined for each of the compounds in each cell line and healthy bone marrow cells following a 4-h incubation. The data indicated that a 16-18 carbon chain at the sn-1 coupled with a short substitution at sn-2 had the broadest antitumor activity and was the least toxic to normal bone marrow cells. The results provide a number of useful leads toward the design and development of potentially more active phospholipid compounds.
开展这项研究是为了阐明抗癌烷基溶血磷脂的结构-功能关系，并评估它们对肿瘤细胞的选择性细胞毒性程度。通过胸腺嘧啶核苷掺入、克隆形成试验以及针对一系列人类白血病细胞系和健康骨髓祖细胞的蛋白激酶C活性影响来测定，对一系列在sn-1和sn-2位具有不同取代基的甘油磷酸胆碱类似物的抑制活性进行了测试。在4小时孵育后，测定了每种化合物在每种细胞系和健康骨髓细胞中的IC50。数据表明，sn-1位的16至18个碳链与sn-2位的短取代基相结合具有最广泛的抗肿瘤活性，并且对正常骨髓细胞的毒性最小。这些结果为设计和开发潜在活性更高的磷脂化合物提供了许多有用的线索。
