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

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

doi:10.1007/s00706-016-1785-8

Edyta Łukowska-Chojnacka, Patrycja Wińska + Show 2 more

Open Access

https://doi.org/10.1007/s00706-016-1785-8

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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.Graphical abstract

Highlights

Azole derivatives have been reported to possess diverse biological activity and are widely used in a medicinal chemistry [1–3]
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-tetrabromo1-(3-chloropropyl)-1H-benzimidazole and 4,5,6,7-tetrabromo-2-(3-chloropropyl)-2H-benzotriazole
It was shown that the attachment of a tetrazolyl substituent to indole derivatives resulted in an increase of both; antibacterial activity against Gram-positive bacteria (Bacillus subtilis, Streptococcus lactis) and Gramnegative bacteria (Escherichia coli, Pseudomonas aeruginosa), and antifungal activity against Candida albicans, Aspergillus niger, and Penicillium sp. [4]