6533b825fe1ef96bd1283232
RESEARCH PRODUCT
Clavines as antitumor agents. 3: Cytostatic activity and structure/activity relationships of 1-alkyl agroclavines and 6-alkyl 6-noragroclavines.
Werner E.g. MüllerA. MaidhofReinhold SiebenE. EichChristoph Beckersubject
MaleDNA polymeraseDNA-Directed DNA PolymeraseLymphocyte ActivationReceptors DopamineMiceStructure-Activity RelationshipDrug DiscoverymedicineAnimalsRNA MessengerRNA NeoplasmErgolinesLeukemia L1210ReceptorAlkylPharmacologychemistry.chemical_classificationAntibiotics AntineoplasticDNA synthesisbiologyDNA NeoplasmIn vitroNeoplasm ProteinsErgolineMechanism of actionchemistryBiochemistryReceptors Serotoninbiology.proteinEffluxmedicine.symptommedicine.drugdescription
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 alpha and beta activities was caused. The mechanism of action seems to be a fundamentally new one for ergoline compounds as interactions with alpha-adrenoceptors, dopamine and 5-hydroxytryptamine receptors are not involved.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 1986-06-01 | The Journal of Antibiotics |