CLAVINES AS ANTITUMOR AGENTS, 3: CYTOSTATIC ACTIVITY AND STRUCTURE/ACTIVITY RELATIONSHIPS OF 1-ALKYL AGROCLAVINES AND 6-ALKYL 6-NORAGROCLAVINES

• Published in: Journal of antibiotics Vol. 39; no. 6; pp. 804 - 812
• Main Authors: EICH, E., BECKER, C., SIEBEN, R., MAIDHOF, A., MÜLLER, W. E. G.
• Format: Journal Article
• Language: English
• Published: Japan JAPAN ANTIBIOTICS RESEARCH ASSOCIATION 1986
• Subjects: Animals; Antibiotics, Antineoplastic - pharmacology; DNA, Neoplasm - biosynthesis; DNA-Directed DNA Polymerase - analysis; Ergolines - pharmacology; Leukemia L1210 - metabolism; Lymphocyte Activation - drug effects; Male; Mice; Neoplasm Proteins - biosynthesis; Receptors, Dopamine - drug effects; Receptors, Serotonin - drug effects; RNA, Messenger - metabolism; RNA, Neoplasm - biosynthesis; Structure-Activity Relationship
• ISSN: 0021-8820; 1881-1469
• DOI: 10.7164/antibiotics.39.804

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-1 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 α and β activities was caused. The mechanism of action seems to be a fundamentally new one for ergoline compounds as interactions with α-adrenoceptors, dopamine and 5-hydroxytryptamine receptors are not involved.