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Anti-Cancer Agents in Medicinal Chemistry


ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Research Article

Hybridized Quinoline Derivatives as Anticancer Agents: Design, Synthesis, Biological Evaluation and Molecular Docking

Author(s): Mohamed R. Selim, Medhat A. Zahran, Amany Belal*, Moustafa S. Abusaif*, Said A. Shedid, Ahmed B.M. Mehany, Gameel A.M. Elhagali and Yousry A. Ammar*

Volume 19 , Issue 4 , 2019

Page: [439 - 452] Pages: 14

DOI: 10.2174/1871520618666181112121058

Price: $65


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.

Keywords: Quinoline, pyrazolone, chromene, thizolidinone, pyridine, pyrimidine, anticancer, caspase-3, tubulin polymerization, cell cycle analysis.

Graphical Abstract
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