Copper is an essential element and has redox potential, thus copper complexes have been developed rapidly with the hope of curing cancer. To further develop anticancer agents and investigate their anticancer mechanisms, two Cu complexes, [Cu(bpbb)·Cl·SCN]·(CHOH) () and [Cu(bpbb)·Br·(OH)] (), were synthesized and characterized using 4,4'-bis((2-(pyridin-2-yl)-1-benzo[]imidazol-1-yl)methyl)biphenyl (bpbb), with associated Cu(ii) salts. Complex is a binuclear structure, whereas is a one-dimensional complex. Compared with , complex exhibited potent cytotoxicity toward four cell lines (HCT116, BGC823, HT29, and SMMC7721), and was most effective against HCT116 cells. Therefore, further in-depth investigation was carried out using complex. Absorption spectral titration experiments, ethidium bromide displacement assays, and circular dichroism spectroscopic studies suggested that complex binds strongly to DNA by intercalation. Complex exhibited a clear concentration-dependent pBR322 DNA cleavage activity. Inductively coupled plasma mass spectrometry testing implied that complex could enter cells and that DNA was one important target. Cellular level assays suggested that complex activates the generation of intracellular reactive oxygen species, causing DNA damage, promoting cell cycle arrest and mitochondria dysfunction, and inducing cellular apoptosis.

A series of 5-aryl-4-(4-arylpiperazine-1-carbonyl)-2H-1,2,3-triazol derivatives were designed as potential microtubule targeting agents. The regioselective alkylation of 5-aryl-4-(4-arylpiperazine-1-carbonyl)-2H-1,2,3-triazole was predicted by computations and confirmed by an unambiguous synthetic route. The antiproliferative activity of the synthesized compounds was tested in vitro using three human cancer cell lines and some compounds exhibited significant antiproliferative activity, which suggested the reasonability of introduction of the 1,2,3-triazole fragment. Among them, compound 7p showed highest activity with the IC50 values at nanomolar level towards all three cell lines, which were comparable to the positive control, CA-4. Tubulin polymerization assay, immunofluorescence studies, cell cycle analysis and competitive tubulin-binding assay strongly proved that 7p is a colchicine binding site inhibitor of tubulin. Thus, 7p was identified as a promising drug candidate for further development of colchicine binding site inhibitors.

No abstract

No abstract

No abstract