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DOI: 10.1055/s-2007-969155
© Georg Thieme Verlag Stuttgart · New York
Clavines as Antitumor Agents; 21,2,3. Natural 8-Hydroxymethyl-ergoline Type Clavines and their Derivatives
1 Dedicated to Dr. Albert Hofmann on the occasion of his 80th. birth day.2 Part 1, see Ref. (7).3 Partial results of the dissertation of C. Becker, Mainz, 1985.Publication History
1985
Publication Date:
26 February 2007 (online)
Abstract
The cytostatic potentials of 16 clavines were determined in the L5178y mouse lymphoma cell system: three of them are natural 8-hydroxymethylergoline type alkaloids (elymoclavine, lysergol, dihydrolysergol-I) and 13 are semisynthetic derivatives (O-acyl-; 1-alkyl-; 1-alkyl-O-acyl-; 1,O-dialkyl-; masked aldehydes). It is shown that in contrast to these alkaloids some of their derivatives are potent cytostatic agents: 1-propylelymoclavine (ED50 cone.: 2.2 µM), 1-propylelymoclavine-O-butyrate (2.7 µM), 6-methyl-8β-(2′-oxo-cyclohexylidenemethyl)-ergoline-I (4.0 µM). O-Acyl derivatives without substitution at N-1 were almost inactive. The substitution of the hydrogen at N-1 of inactive clavines by an alkyl group with three carbon atoms led to very active compounds indicating that the nature of the substituent at N-1 is very important for cytostatic activity. Incorporation studies in the presence of 1-propylelymoclavine showed that this compound inhibits primarily DNA synthesis. Partial syntheses of new ergolines are described.