Clavines. New antibiotics with cytostatic activity.
The cytostatic potentials of ten ergolines were determined in the L5178y mouse lymphoma cell system; six of them belong to the clavines (agroclavine, 1-propyl-agroclavine, 1-propyl-festuclavine, 1-allyl-festuclavine, 6-cyano-6-nor-festuclavine and 1-hydroxymethyl-festuclavine) and four to the lysergic acid derivatives (methylergometrine, lysergic acid amide, isolysergic acid amide and lysergic acid diethylamide). It is shown that agroclavine (ED50: 3.9 microM), 1-propyl-agroclavine (3.5 microM), 1-propylfestuclavine (4.3 microM) and 1-allyl-festuclavine (4.3 microM) are potent cytostatic agents. Up to 2 X ED50 concentration the inhibitory effect was completely reversible. Incorporation studies suggested that the compounds inhibit DNA synthesis; this assumption was also supported by the findings which revealed that after incubation with these clavines, the cells showed slight 'unbalanced growth'. 6-Cyano-6-nor-festuclavine was less inhibitory (ED50 11.8 microM). 1-Hydroxymethyl-festuclavine and all lysergic acid derivatives tested were without any detectable activity.
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004873:Ergolines / Q000494:pharmacology*; D007940:Leukemia L5178 / Q000188:drug therapy; D051379:Mice; D012313:RNA / Q000096:biosynthesis; D013329:Structure-Activity Relationship
D000903:Antibiotics, Antineoplastic; D004873:Ergolines; D012313:RNA; D004247:DNA