title: 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.
authors.affiliation: Dipartimento di Scienze del Farmaco, Universitá degli Studi di Padova, via Marzolo 5, 35131 Padova, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Marzaro
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza Universitá di Roma, Piazzale Aldo Moro 5, I-00185 Roma, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Coluccia
authors.affiliation: Dipartimento di Scienze del Farmaco, Universitá degli Studi di Padova, via Marzolo 5, 35131 Padova, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ferrarese
authors.affiliation: Department of Molecular Medicine, University of Padova, via Gabelli 63, 35121 Padova, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Brun
authors.affiliation: Department of Molecular Medicine, University of Padova, via Gabelli 63, 35121 Padova, Italy.
authors.forename: Ignazio
authors.initials: I
authors.lastname: Castagliuolo
authors.affiliation: Dipartimento di Scienze del Farmaco, Universitá degli Studi di Padova, via Marzolo 5, 35131 Padova, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Conconi
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza Universitá di Roma, Piazzale Aldo Moro 5, I-00185 Roma, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: La Regina
authors.affiliation: Screening Technologies Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702, United States.
authors.forename: Ruoli
authors.initials: R
authors.lastname: Bai
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza Universitá di Roma, Piazzale Aldo Moro 5, I-00185 Roma, Italy.
authors.forename: Romano
authors.initials: R
authors.lastname: Silvestri
authors.affiliation: Screening Technologies Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702, United States.
authors.forename: Ernest
authors.initials: E
authors.lastname: Hamel
authors.affiliation: Dipartimento di Scienze del Farmaco, Universitá degli Studi di Padova, via Marzolo 5, 35131 Padova, Italy.
authors.forename: Adriana
authors.initials: A
authors.lastname: Chilin
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D050257:Tubulin Modulators / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D050257:Tubulin Modulators; D011505:Protein-Tyrosine Kinases