Synthesis and Biological Evaluation of 2-Substituted Quinazolin-4(3<i>H</i>)-Ones with Antiproliferative Activities
Maria Karelou,
Dionysis Kampasis,
Amalia D. Kalampaliki,
Leentje Persoons,
Andreas Krämer,
Dominique Schols,
Stefan Knapp,
Steven De Jonghe,
Ioannis K. Kostakis
Affiliations
Maria Karelou
Department of Pharmacy, Division of Pharmaceutical Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Zografou, 15771 Athens, Greece
Dionysis Kampasis
Department of Pharmacy, Division of Pharmaceutical Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Zografou, 15771 Athens, Greece
Amalia D. Kalampaliki
Department of Pharmacy, Division of Pharmaceutical Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Zografou, 15771 Athens, Greece
Leentje Persoons
Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, KU Leuven, Herestraat 49, P.O. Box 1043, 3000 Leuven, Belgium
Andreas Krämer
Institute for Pharmaceutical Chemistry, Department of Biochemistry, Chemistry and Pharmacy, Goethe University Frankfurt, Max-von-Laue-Straße 9, 60438 Frankfurt, Germany
Dominique Schols
Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, KU Leuven, Herestraat 49, P.O. Box 1043, 3000 Leuven, Belgium
Stefan Knapp
Institute for Pharmaceutical Chemistry, Department of Biochemistry, Chemistry and Pharmacy, Goethe University Frankfurt, Max-von-Laue-Straße 9, 60438 Frankfurt, Germany
Steven De Jonghe
Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, KU Leuven, Herestraat 49, P.O. Box 1043, 3000 Leuven, Belgium
Ioannis K. Kostakis
Department of Pharmacy, Division of Pharmaceutical Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Zografou, 15771 Athens, Greece
Sixteen new 2-substituted quinazolines were synthesized using a straightforward methodology starting from 2-methoxybezoic acid or 3-methoxy-2-naphthoic acid. The anti-proliferative activity of the target compounds was evaluated against nine cancer cell lines. Additionally, all the compounds were screened for their potency and selectivity against a panel of 109 kinases and four bromodomains, using Differential Scanning Fluorimetry (DSF). Compound 17 bearing a 2-methoxyphenyl substitution along with a basic side chain displayed a remarkable profile against the majority of the tested cell lines.
