Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 20, HR-10000, Zagreb, Croatia.
Department of Chemistry and Biochemistry, Faculty of Veterinary Medicine, University of Zagreb, Heinzelova 55, HR-10000, Zagreb, Croatia.
Eur J Med Chem. 2019 Jul 1;173:63-75. doi: 10.1016/j.ejmech.2019.04.007. Epub 2019 Apr 7.
The novel benzimidazol-2-yl-fur-5-yl-(1,2,3)-triazolyl dimeric series with aliphatic and aromatic central linkers was successfully prepared with the aim of assessing binding affinity to DNA/RNA and antitrypanosomal activity. UV-Visible spectroscopy, thermal denaturation showed interaction of heterocyclic bis-amidines with ctDNA. Circular dichroism studies indicated uniform orientation of heterocyclic bis-amidines along the chiral double helix axis, revealing minor groove binding as the dominant binding mode. The amidino fragment and 1,4-bis(oxymethylene)phenyl spacer were the main determinants of activity against Trypanosoma brucei. The bis-benzimidazole imidazoline 15c, which had antitrypanosomal potency in the submicromolar range and DNA interacting properties, emerged as a candidate for further structural optimization to obtain more effective agents to combat trypanosome infections.
新型苯并咪唑-2-基-呋喃-5-基-(1,2,3)-三唑二聚体系列，具有脂肪族和芳香族中心连接体，成功制备，旨在评估与 DNA/RNA 的结合亲和力和抗锥虫活性。紫外可见光谱、热变性显示杂环双脒与 ctDNA 的相互作用。圆二色性研究表明，杂环双脒沿手性双螺旋轴均匀取向，表明小沟结合是主要的结合模式。脒基片段和 1,4-双(氧亚甲基)苯间隔基是对抗布氏锥虫活性的主要决定因素。具有亚微摩尔范围内抗锥虫活性和 DNA 相互作用特性的双苯并咪唑咪唑啉 15c，作为进一步结构优化的候选药物，以获得更有效的抗锥虫感染药物。
