C-12-substituted indolo[2,1-a]isoquinolines as estrogen receptor affinic cytostatic agents.

Methoxysubstituted 5,6-dihydro-indolo[2,l-a]isoquinolines with a methyl (2b-f) or a formyl group at C-12 (4a-f) and 12,12-dimethylisoquinolinium salts (3b-f) were synthesized and tested for cytostatic activity in vitro. The tetramethoxy-indoloisoquinoline 4f was the most active derivative in the P 388 Dl leukemia cell line, whereas compounds with two methoxy groups (4a, 4b) were more potent against the M D A M B 231 mammary tumor cells. The tetraacetoxy-12-formyl-5,6-dihydro-indoloisoquinoline 9 has proven to be active in both cell lines (T/C = 5 %). In vivo it increased the life span of mice with P 388 leukemia (T/C = 133 %). The acetates 7 and 8 exhibited binding affinities for the estrogen receptor, but did not exert a selective action on hormone-dependent M C F 7 cells. In 12-Stellung substituierte Indolo[2,l-a]isochinoline als östrogenrezeptoraffine Cytostatika