Synthesis of polybrominated benzimidazole and benzotriazole derivatives containing a tetrazole ring and their cytotoxic activity

Edyta Łukowska-Chojnacka; Patrycja Wińska; Monika Wielechowska; Maria Bretner

doi:10.1007/s00706-016-1785-8

Synthesis of polybrominated benzimidazole and benzotriazole derivatives containing a tetrazole ring and their cytotoxic activity

Monatsh Chem. 2016;147(10):1789-1796. doi: 10.1007/s00706-016-1785-8. Epub 2016 Jun 14.

Authors

Edyta Łukowska-Chojnacka¹, Patrycja Wińska¹, Monika Wielechowska¹, Maria Bretner¹

Affiliation

¹ Faculty of Chemistry, Institute of Biotechnology, Warsaw University of Technology, Noakowskiego St. 3, 00-664 Warsaw, Poland.

Abstract

Abstract: A series of new benzimidazole and benzotriazole derivatives containing a tetrazole moiety was synthesized by N-alkylation of 5-aryltetrazole with 4,5,6,7-tetrabromo-1-(3-chloropropyl)-1H-benzimidazole and 4,5,6,7-tetrabromo-2-(3-chloropropyl)-2H-benzotriazole. The reaction was regioselective and mostly 2,5-disubstituted tetrazole derivatives were obtained. The effect of all synthesized compounds on human recombinant casein kinase 2alpha subunit (rhCK2α) and cytotoxicity against human T-cell lymphoblast (CCRF-CEM) and breast adenocarcinoma (MCF-7) cell lines were evaluated. The results have shown that many of the synthesized compounds exhibit significant cytotoxicity at micromolar concentration.

Keywords: Antitumor agents; Azole; Benzimidazole; Heterocycles; Tetrazole; Total synthesis.