Abstract
In this study, a variety of original ligands related to Combretastatin A-4 and isoCombretastatin A-4, able to inhibit the tubulin polymerization into microtubules, was designed, synthesized, and evaluated. Our lead compound 15d having a quinazoline as A-ring and a 2-substituted indole as B-ring separated by a N-methyl linker displayed a remarkable sub-nanomolar level of cytotoxicity (IC50 < 1 nM) against 9 human cancer cell lines.
Keywords:
Cancer; Cytotoxicity; Indole; Oxazinoindole; Pyridoindole; Quinazoline; Tubulin; isoCA-4.
Copyright © 2021 Elsevier Masson SAS. All rights reserved.
MeSH terms
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Animals
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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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Binding Sites
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Cell Cycle Checkpoints / drug effects
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Drug Resistance, Neoplasm / drug effects
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Drug Screening Assays, Antitumor
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Drug Stability
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Humans
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Indoles / chemistry*
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Indoles / metabolism
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Indoles / pharmacology
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Microsomes, Liver / metabolism
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Molecular Docking Simulation
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Rats
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Stilbenes / chemistry*
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Stilbenes / metabolism
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Stilbenes / pharmacology
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Structure-Activity Relationship
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Tubulin / chemistry
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Tubulin / metabolism
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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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Indoles
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Stilbenes
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Tubulin
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Tubulin Modulators
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fosbretabulin