Synthesis and structure-activity relationship studies of cytotoxic epoxide derivatives of 7-oxabicyclo[2.2.1]heptane.
Dimethyl exo-5,6-oxido-7-oxabicyclo[2.2.1]hept-2-ene-2,3-dicarboxylate (1) and the 1-methyl homologue 2 were shown to exhibit significant cytotoxicity in the 9KB tissue culture assay. Several analogues of 1 were prepared and it was found that removal of the epoxide, or the oxygen bridge, or the 2,3 double bond from 1 resulted in loss of significant cytotoxic activity. One compound which lacked the epoxide moiety, dimethyl 1-methyl-7-oxabicyclo[2.2.1]hepta-2,5-diene-2,3-dicarboxylate (5), also exhibited marginal cytotoxic activity.
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D001952:Bridged-Ring Compounds / Q000138:chemical synthesis*; D002470:Cell Survival / Q000187:drug effects; D046508:Culture Techniques; D004852:Epoxy Compounds / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D008815:Mice, Inbred Strains; D013329:Structure-Activity Relationship; D013885:Thiosulfates
D000970:Antineoplastic Agents; D001643:Bridged Bicyclo Compounds; D001952:Bridged-Ring Compounds; D004852:Epoxy Compounds; D013885:Thiosulfates