Aims: Tyrosine kinases and topoisomerase I are common target enzymes for the majority of the anticancer
agents. In contrast to quinazolines and quinolines, kinase inhibitors and topoisomerase inhibitors incorporating
cinnoline scaffold are relatively infrequent. Thus the aim of this work was to replace the former scaffolds
with the latter one. Eighteen novel cinnoline derivatives were designed, synthesized and characterized
using both microanalytical and spectral data.
Methods: The cytotoxic activity of the new compounds was screened in vitro against both human breast cancer
cells and normal breast cells.
Results: The enzymatic inhibition activity of promising candidates against both epidermal growth factor receptor
tyrosine kinase and topoisomerase I was accomplished.
Conclusions: Cell cycle profiles were observed at IC50 doses of representative biologically active compounds.
Compound 7 represented a new scaffold incorporating triazepinocinnoline ring system and showed outstanding
cytotoxic activity against MCF-7 (0.049 µM), tyrosine kinase inhibition (0.22 µM), apoptosis percentage and the
highest selectivity index.