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Synthesis of Antitumor‐Active Betulinic Acid‐Derived Hydroxypropargylamines by Copper‐Catalyzend Mannich Reactions
Author(s) -
Csuk René,
Nitsche Christoph,
Sczepek Ronny,
Schwarz Stefan,
Siewert Bianka
Publication year - 2013
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.201200428
Subject(s) - chemistry , mannich base , propidium iodide , sulforhodamine b , cytotoxicity , mannich reaction , betulin , acridine orange , betulinic acid , organic chemistry , combinatorial chemistry , biochemistry , apoptosis , programmed cell death , catalysis , biology , in vitro , genetics
Several novel betulin derivates were prepared using Mannich reactions as a key step. Starting from 3‐ethynyl‐3‐hydroxy‐lup‐20(29)‐ene derivatives, copper‐catalyzed Mannich reactions yielded hydroxypropargyl ammonium hydrochlorides or their corresponding methiodides. All compounds were screened in a sulforhodamine B assay for their antitumor activity using a panel of 9 human cancer cell lines. Some of these compounds showed significant cytotoxicity; they act by triggering apoptotic cell death as shown by additional acridine orange/propidium iodide assays, Trypan blue tests, DNA laddering experiments, and investigations of the cell cycle.