Antitumor agents. 16. Steroidal alpha-methylene-gamma-lactones.
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.
D000731:Androstanes / Q000138:chemical synthesis* / Q000627:therapeutic use; D000736:Androstenes / Q000138:chemical synthesis / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D002279:Carcinoma 256, Walker / Q000188:drug therapy; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy; D002294:Carcinoma, Squamous Cell; D002460:Cell Line; D006801:Humans; D007783:Lactones / Q000138:chemical synthesis* / Q000627:therapeutic use; D007822:Laryngeal Neoplasms; D007939:Leukemia L1210 / Q000188:drug therapy; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D051381:Rats; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000627:therapeutic use
D000731:Androstanes; D000736:Androstenes; D000970:Antineoplastic Agents; D007783:Lactones; D013141:Spiro Compounds