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Synthesis and biological activity of newly designed 2-benzothienyl and 2-bithieny amidino-substituted benzazole derivatives

It is well known that cationic amidines, placed usually at the termini of the molecule, are structural parts of numerous compounds of biological interest. Their main function is the interaction with potential biological targets and formation of the stable complex with biological molecules. On the other hand, benzimidazoles and benzothiazoles as one of the most important heterocyclic nitrogen scaffolds have great biological importance and thus become unavoidable structural motifs in the rational design of novel drugs. In our recent studies we have proved that by engrafting amidine extremities as positively charged substituents at the end of the heteroaromatic substructures we could significantly improve the antiproliferative [1, 2] as well as antitrypanosomal activities [3]. Herein we present the synthesis of newly designed 2-benzothienyl and 2-bithienyl benzimidazole/benzothiazole derivatives bearing either acyclic unsubstituted and isopropyl amidine moiety, as well as cyclic 2-imidazolinyl and 3, 4, 5, 6-tetrahydropyrimidin-2-yl amidine moiety. All prepared compounds were tested for their antiproliferative activity on six human cancer cell lines (HCT116, H460, MCF-7, PC3, HeLa, SW620) and non-tumour cell line HEK 293, while antitrypanosomal activity was tested on protozoan parasite Trypanosoma brucei. Some of tested compounds showed strong and selective antiproliferative activity against H 460 cells in submicromolar range of inhibitory concentrations. Obtained results revealed that benzothiazole derivatives were more active in comparison to their benzimidazole analogues. Additionally, we can conclude that also the type of the amidine group has strong influence on the biological activity.

benzothiazole; benzimidazole; amidine; synthesis; biological activity

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