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Discovery of biarylaminoquinazolines as novel tubulin polymerization inhibitors.

ABSTRACT: Cell cycle experiments with our previously reported 4-biphenylaminoquinazoline (1-3) multityrosine kinase inhibitors revealed an activity profile resembling that of known tubulin polymerization inhibitors. Novel 4-biarylaminoquinazoline analogues of compound 2 were synthesized and evaluated as inhibitors of several tyrosine kinases and of tubulin. Although compounds 1-3 acted as dual inhibitors, the heterobiaryl analogues possessed only anti-tubulin properties and targeted the colchicine site. Furthermore, molecular modeling studies allowed the rationalization of the pharmacodynamic properties of the compounds.

SUBMITTER: Marzaro G

PROVIDER: S-EPMC4086859 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Discovery of biarylaminoquinazolines as novel tubulin polymerization inhibitors.

Marzaro Giovanni G Coluccia Antonio A Ferrarese Alessandro A Brun Paola P Castagliuolo Ignazio I Conconi Maria Teresa MT La Regina Giuseppe G Bai Ruoli R Silvestri Romano R Hamel Ernest E Chilin Adriana A

Journal of medicinal chemistry 20140514 11

Cell cycle experiments with our previously reported 4-biphenylaminoquinazoline (1-3) multityrosine kinase inhibitors revealed an activity profile resembling that of known tubulin polymerization inhibitors. Novel 4-biarylaminoquinazoline analogues of compound 2 were synthesized and evaluated as inhibitors of several tyrosine kinases and of tubulin. Although compounds 1-3 acted as dual inhibitors, the heterobiaryl analogues possessed only anti-tubulin properties and targeted the colchicine site. F ...[more]

PMID: 24801610

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Novel indole-bearing combretastatin analogues as tubulin polymerization inhibitors.

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Design, synthesis and molecular docking of novel diarylcyclohexenone and diarylindazole derivatives as tubulin polymerization inhibitors.

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