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Synthesis and Antiproliferative Activity of Some Ellipticine‐Like 11 H ‐Pyrido[ a ]carbazole Derivatives
Author(s) -
Ferlin Maria Grazia,
Gia Ornella,
Dalla Via Lisa
Publication year - 2011
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201100233
Subject(s) - topoisomerase , stereochemistry , chemistry , cytotoxicity , dna , carbazole , indole test , cell culture , structure–activity relationship , side chain , biochemistry , in vitro , biology , organic chemistry , polymer , genetics
Some modified 11 H ‐pyrido[ a ]carbazoles (11 H ‐PyC) and their corresponding tetrahydro derivatives (11 H ‐THPyC) were prepared. A common multistep pathway characterized by conventional reactions, including a Fischer‐indole‐type synthesis, yielded the tetracyclic compounds. To improve cytotoxicity, 11 H ‐PyC and 11 H ‐THPyC derivatives were endowed with a diethylaminoethyl side chain. The antiproliferative activity was assessed in three human tumor cell lines, and a number of derivatives showed a cytotoxic effect in agreement with their capacity to form a molecular intercalative complex with DNA and to interfere with the relaxation activity of DNA topoisomerase II. In contrast, three derivatives that exhibited significant antiproliferative efficacy, showed no inhibition of topoisomerase II, thus suggesting an unexpected and novel mode of action for these ellipticine‐like compounds independent of topoisomerase II activity.