Abstract
The synthesis and evaluation of a new series of IsoCombretaQuinolines (IsoCoQuines) 2 with a 2-substituted-quinoline in place of the 3,4,5-trimethoxyphenyl ring present in isoCA-4 and CA-4 are described. Most of these compounds displayed a potent cytotoxic activity (IC50 < 10 nM) against a panel of five human cancer cell lines and inhibited tubulin assembly at a micromolar level. The most potent analogue 2b, having a 3-hydroxy-4-methoxyphenyl as B-ring, led to cell cycle arrest in G2/M phase. Docking studies indicate that 2b showed a binding mode comparable to those previously observed with quinazoline analogous (IsoCoQ) and with isoCA-4 at the colchicine binding site of tubulin.
Keywords:
Binding; Cancer; Cytotoxicity; Quinoline; Tubulin; isoCA-4.
Copyright © 2016 Elsevier Masson SAS. All rights reserved.
MeSH terms
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / metabolism
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Antineoplastic Agents / pharmacology
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Apoptosis / drug effects
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Chemistry Techniques, Synthetic
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Drug Design*
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Drug Screening Assays, Antitumor
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G2 Phase Cell Cycle Checkpoints / drug effects
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Humans
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M Phase Cell Cycle Checkpoints / drug effects
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Molecular Docking Simulation
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Protein Multimerization / drug effects*
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Protein Structure, Quaternary
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Quinazolines / chemical synthesis*
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Quinazolines / chemistry
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Quinazolines / metabolism
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Quinazolines / pharmacology*
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Tubulin / chemistry*
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Tubulin / metabolism
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Tubulin Modulators / chemical synthesis*
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Tubulin Modulators / chemistry
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Tubulin Modulators / metabolism
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Tubulin Modulators / pharmacology*
Substances
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Antineoplastic Agents
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Quinazolines
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Tubulin
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Tubulin Modulators