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.
Design, Synthesis and Biological Evaluation of 1,4-Disubstituted-3,4-dihydroisoquinoline Compounds as New Tubulin Polymerization Inhibitors