Lee K H, Ibuka T, Kim S H, Vestal B R, Hall I H, Huang E S
J Med Chem. 1975 Aug;18(8):812-7. doi: 10.1021/jm00242a010.
Several novel steroidal alpha-methylene-gamma-lactones and related derivatives have been synthesized as potential steroid alkylating antitumor agents. The synthesis of these compounds involved the convenient Reformatsky-type reaction between ethyl-alpha-(bromomethyl)acrylate and the proper steroidal ketones. In vitro assay for the cytotoxicity of these compounds against the growth of tissue culture cells originating from human epidermoid carcinoma of the larynx (H.Ep.-2) has shown significant activity. Cytotoxicity was improved at least sixfold with the introduction of lipophilic steroidal character. Preliminary in vivo tumor assay also indicated that these compounds were active against Walker 256 carcinosarcoma in rats and were inactive against both L1210 lymphoid leukemia and Ehrlich ascites carcinoma in mice. However, the simple alpha-methylene-beta,beta-dicarbethoxy-gamma-butyrolactone significantly inhibited Ehrlich ascites tumor growth.
已经合成了几种新型甾体α-亚甲基-γ-内酯及其相关衍生物，作为潜在的甾体烷基化抗肿瘤剂。这些化合物的合成涉及α-（溴甲基）丙烯酸乙酯与适当的甾体酮之间简便的Reformatsky型反应。对这些化合物针对源自人喉表皮样癌（H.Ep.-2）的组织培养细胞生长的细胞毒性进行的体外测定显示出显著活性。引入亲脂性甾体特性后，细胞毒性至少提高了六倍。初步的体内肿瘤测定还表明，这些化合物对大鼠的Walker 256癌肉瘤有活性，而对小鼠的L1210淋巴细胞白血病和艾氏腹水癌均无活性。然而，简单的α-亚甲基-β，β-二乙氧基-γ-丁内酯能显著抑制艾氏腹水肿瘤的生长。
