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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Antineoplastic Agents / chemical synthesis*
-
Antineoplastic Agents / chemistry
-
Antineoplastic Agents / pharmacology
-
Cell Line, Tumor
-
Drug Resistance, Multiple
-
Drug Resistance, Neoplasm
-
Drug Screening Assays, Antitumor
-
Humans
-
Molecular Docking Simulation
-
Molecular Dynamics Simulation
-
Protein-Tyrosine Kinases / antagonists & inhibitors*
-
Quinazolines / chemical synthesis*
-
Quinazolines / chemistry
-
Quinazolines / pharmacology
-
Structure-Activity Relationship
-
Tubulin Modulators / chemical synthesis*
-
Tubulin Modulators / chemistry
-
Tubulin Modulators / pharmacology
Substances
-
Antineoplastic Agents
-
Quinazolines
-
Tubulin Modulators
-
Protein-Tyrosine Kinases