C‐12‐Substituted Indolo[2,1‐a]Isoquinolines as Estrogen Receptor Affinic Cytostatic Agents

Methoxysubstituted 5,6‐dihydro‐indolo[2,1‐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 D1 leukemia cell line, whereas compounds with two methoxy groups (4a, 4b) were more potent against the MDA‐MB 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 MCF‐7 cells.