Amino- and polyaminophthalazin-1(2 H)-ones: synthesis, coordination properties, and biological activity

Zbigniew Malinowski; Emilia Fornal; Agata Sumara; Renata Kontek; Karol Bukowski; Beata Pasternak; Dariusz Sroczyński; Joachim Kusz; Magdalena Małecka; Monika Nowak

doi:10.3762/bjoc.17.50

Amino- and polyaminophthalazin-1(2 H)-ones: synthesis, coordination properties, and biological activity

Beilstein J Org Chem. 2021 Feb 25:17:558-568. doi: 10.3762/bjoc.17.50. eCollection 2021.

Authors

Affiliations

¹ Department of Organic Chemistry, Faculty of Chemistry, University of Lodz, Tamka 12, 91-403 Łódź, Poland.
² Department of Pathophysiology, Medical University of Lublin, Jaczewskiego 8b, 20-090 Lublin, Poland.
³ Department of Molecular Biotechnology and Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Banacha 12/16, 90-237 Łódź, Poland.
⁴ Laboratory of Molecular Spectroscopy, Faculty of Chemistry, University of Lodz, Tamka 12, 91-403 Łódź, Poland.
⁵ Department of Inorganic and Analytical Chemistry, Faculty of Chemistry, University of Lodz, Tamka 12, 91-403 Łódź, Poland.
⁶ Institute of Physics, University of Silesia, 75 Pułku Piechoty 1, 41-500 Chorzów, Poland.
⁷ Department of Physical Chemistry, Theoretical and Structural Chemistry Group, Faculty of Chemistry, University of Lodz, Pomorska 163/165, 90-236 Łódź, Poland.

Abstract

Amino- and polyaminophthalazinones were synthesized by the palladium-catalyzed amination (alkyl- and arylamines, polyamines) of 4-bromophthalazinones in good yields. The coordinating properties of selected aminophthalazinones towards Cu(II) ions were investigated and the participation of the nitrogen atoms in the complexation of the metal ion was shown. A biological screening of the potential cytotoxicity of selected synthesized compounds on HT-29 and PC-3 cell lines, as well as on the L-929 cell line, proved that some amino derivatives of phthalazinone show interesting anticancer activities. The detailed synthesis, spectroscopic data, and biological assays are reported.

Keywords: Pd cross-coupling; amination; complexes; cytotoxicity; phthalazinone.

Grants and funding

The authors are grateful to the University of Lodz for a partial financial support. This research was supported in part by PLGrid Infrastructure.