Clavines as antitumor agents, 3; cytostatic activity and structure/activity relationships of 1-alkyl agroclavines and 6-alkyl 6-noragroclavines

Abstract

The cytostatic potential of twenty antibiotic agroclavines has been examined in the L5178y mouse lymphoma cell system. Twelve of these compounds are described for the first time. It is shown that the substituent at N-l of agroclavine is very important whereas the substituent at N-6 is of less influence if it is not hydrogen. Incorporation studies in the presence of 1-propylagroclavine suggest that DNA synthesis in the lymphoma cells is inhibited. The effect on the corresponding [3H]thymidine incorporation in murine spleen lymphocytes is comparably low. Neither a significant change of mRNA efflux nor of DNA polymerase a and β activities was caused. The mechanism of action seems to be a fundamentally new one for ergoline compounds as interactions with a-adrenoceptors, dopamine and 5-hydroxy-tryptamine receptors are not involved. © 1986, JAPAN ANTIBIOTICS RESEARCH ASSOCIATION. All rights reserved.