Premium
Synthesis, Cytotoxic, and Antitumor Activities of 2‐Pyridylhydrazones Derived from 3‐Benzoylpyridazines
Author(s) -
Easmon Johnny,
Pürstinger Gerhard,
Heinisch Gottfried,
Fiebig Hans H.,
Roth Thomas,
Hofmann Johann
Publication year - 2014
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.201400137
Subject(s) - clonogenic assay , chemistry , stereochemistry , cytotoxic t cell , ic50 , in vivo , tumor cells , cytotoxicity , nuclear magnetic resonance spectroscopy , cell culture , in vitro , biochemistry , cancer research , biology , genetics , microbiology and biotechnology
A series of 2‐pyridylhydrazones derived from phenyl‐pyridazin‐3‐yl‐methanones were prepared in search for potential novel antitumor agents. The stereochemistry of these compounds was established by means of NMR spectroscopy. Whereas hydrazones derived from 3‐benzoylpyridazines (IC 50 = 0.99–8.74 µM) inhibited the proliferation of the tumor cell lines tested, the non‐fully aromatic 3‐benzoylpyridazinone hydrazones (IC 50 > 10 µM) turned out to be inactive. Compounds E ‐ 1b (IC 50 = 0.12 µM) and E ‐ 1d (IC 50 = 0.18 µM) exert high cytotoxic activities in clonogenic assays involving human tumor cells of different tissue origins. In vivo application of compound E ‐ 1b (300 mg/kg/day) resulted in a 66% reduction in tumor burden.
Accelerating Research
Robert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom
Address
John Eccles HouseRobert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom