Alkaloids of Vinca rosea L. (Catharanthus roseus G. Don). 38. 4'-Dehydrated derivatives.
A series of 4'-dehydrated derivatives of various dimeric Vinca alkaloids has been synthesized to further define the structure-activity relationships of Vinca alkaloids with onolytic potency. The concentrated sulfuric acid dehydration in most cases gave mixtures of the 3',4'-and two isomeric 4',20'-alkenes, which were isolated and characterized primarily by proton and 13C NMR. Compound tested for antitumor activity include the three dehydro isomers of 4'-deacetylvinblastine, 4-deacetylvincristine, and 4-deacetylvinblastine-23-amide and some4'-dehydrated derivatives epimeric at C-18'. Generally, the decrease in toxicity imparted by the new double bond was accompained by a decrease in potency. An exception was 3',4'-dehydro-4-deacetylvincristine, which showed a decrease in toxicity and increase in potency against at least one tumor in which vincristine itself has little effect.
D000230:Adenocarcinoma / Q000188:drug therapy; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000627:therapeutic use; D002478:Cells, Cultured; D007942:Leukemia, Experimental / Q000188:drug therapy; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy; D008545:Melanoma / Q000188:drug therapy; D008722:Methods; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008938:Mitosis / Q000187:drug effects; D008968:Molecular Conformation; D009374:Neoplasms, Experimental / Q000188:drug therapy; D013329:Structure-Activity Relationship; D014748:Vinca Alkaloids / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use
D000972:Antineoplastic Agents, Phytogenic; D014748:Vinca Alkaloids