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C‐12‐Substituted Indolo[2,1‐a]Isoquinolines as Estrogen Receptor Affinic Cytostatic Agents
Author(s) -
Ambros Reinhard,
Von Angerer Silvia,
Wiegrebe Wolfgang
Publication year - 1988
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.19883211010
Subject(s) - in vivo , chemistry , in vitro , stereochemistry , estrogen receptor , cell culture , leukemia , chemical synthesis , biological activity , estrogen , receptor , pharmacology , biochemistry , medicine , biology , endocrinology , cancer , breast cancer , genetics , microbiology and biotechnology
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 D 1 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.