Objective:
Conjugating quinolones with different bioactive pharmacophores to obtain potent anticancer
active agents.
Methods:
Fused pyrazolopyrimidoquinolines 3a-d, Schiff bases 5, 6a-e, two hybridized systems: pyrazolochromenquinoline
7 and pyrazolothiazolidinquinoline 8, different substituted thiazoloquinolines 13-15 and
thiazolo[3,2-a]pyridine derivatives 16a-c were synthesized. Their chemical structures were characterized
through spectral and elemental analysis, cytotoxic activity on five cancer cell lines, caspase-3 activation, tubulin
polymerization inhibition and cell cycle analysis were evaluated.
Results:
Four compounds 3b, 3d, 8 and 13 showed potent activity than doxorubicin on HCT116 and three compounds
3b, 3d and 8 on HEPG2. These promising derivatives showed increase in the level of caspase-3. The
trifloromethylphenyl derivatives of pyrazolopyrimidoquinolines 3b and 3d showed considerable tubulin polymerization
inhibitory activity. Both compounds arrested cell cycle at G2/M phase and induced apoptosis.
Conclusion:
Compounds 3b and 3d can be considered as promising anticancer active agents with 70% of colchicine
activity on tubulin polymerization inhibition and represent hopeful leads that deserve further investigation
and optimization.
The Design, Synthesis, and Evaluation of Coumarin Ring Derivatives of the Novobiocin Scaffold that Exhibit Antiproliferative Activity