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Antiestrogenic Activities of 3,8‐Dihydroxy‐6,11‐dihydrobenzo[a]carbazoles with Sulfur‐Containing Side Chains
Author(s) -
Golob Thomas,
Biberger Christian,
Walter Georg,
von Angerer Erwin
Publication year - 2000
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 - 10.1002/1521-4184(20009)333:9<305::aid-ardp305>3.0.co;2-q
Subject(s) - side chain , chemistry , carbazole , potency , stereochemistry , agonist , indole test , in vivo , structure–activity relationship , ic50 , in vitro , biochemistry , receptor , organic chemistry , microbiology and biotechnology , biology , polymer
The objective of this study was to explore whether the conversion of the 2‐phenylindole system into the tetracyclic benzo[ a ]carbazole changes the endocrine profile when the side chain structure was kept constant. Five different sulfur‐containing side chains were linked to the nitrogen of the tetracycle. The biological evaluation revealed that the character of the indole derivatives remained unchanged after the conversion to the respective benzocarbzoles but the potency decreased by one order of magnitude. In vitro , all derivatives acted as pure antiestrogens without any agonist activity. They strongly inhibited the growth of estrogen‐sensitive MCF‐7 breast cancer cells with IC 50 ‐values in the nanomolar range. In the mouse uterine weight test, the derivatives with an aliphatic side chain were devoid of estrogenic activity and antagonized the effect of estradiol. The presence of an aromatic ring in the side chain gave rise to significant agonist activity in vivo independently of the carrier structure. All data revealed the equivalence of both carrier structures in respect to the endocrine profile but showed a decrease in potency upon the conversion of the 2‐phenylindole system into the benzocarbazole structure.