4,5,14-Triacetylberkeylactone F

1H-imidazole [4,5-f][1,10] phenanthroline is a promising chemical structure for cancer treatment. Herein, we synthesized a novel 1H-imidazole [4,5-f][1,10] phenanthroline derivative named IPM714 and found it exhibited selectively colorectal cancer (CRC) cells inhibitory activities, with half maximal inhibitory concentration (IC50) of 1.74 μM and 2 μM in HCT116 cells and SW480 cells, respectively. The present study is intended to explore the cytotoxicity of IPM714 in cancer cells of various types and its anticancer mechanism in vitro. Cellular functional analyses indicated IPM714 can arrest HCT116 cell cycle in S phase and induce apoptosis in HCT116 and SW480 cells. Western blot and molecular docking showed that IPM714 may suppress PI3K/AKT/mTOR pathway to inhibit cell proliferation and regulate cell cycle as well as apoptosis. This study proved IPM714 to be a promising drug in CRC therapy.

In this paper, the DNA interaction properties of four Ru(ii) polypyridyl complexes, [Ru(bpy)2(pip)]2+ (1), bpy = 2,2'-bipyridine, pip = 2-phenyl-imidazo[4,5-f][1,10]phenanthroline, [Ru(bpy)2(nip)]2+ (2), nip = 2-naphthyl-imidazo[4,5-f][1,10]phenanthroline, [Ru(bpy)2(aip)]2+ (3), aip = 2-(9-anthryl)-imidazo[4,5-f][1,10]phenanthroline and [Ru(bpy)2(pyip)]2+ (4), pyip = 2-(1-pyrenyl)-imidazo[4,5-f][1,10]phenanthroline, were investigated by spectral titration. The intensity increases in the MLCT band of the complexes and the decrease in absorption due to the DNA secondary structure was attributed to DNA condensation by these complexes. The DNA condensing behavior of these complexes was investigated in more detail by gel electrophoresis (GAR), dynamic light scattering (DLS), zeta potential, atomic force microscopy (AFM), and transmission electron microscopy (TEM). The results suggest that the concentration of the complex plays a critical role in its DNA intercalating and DNA condensing behavior. Meanwhile, the aryl units in the ligands of complex 1-4 also have a large effect on their interactions with DNA.

Cells govern their homeostasis through autophagy by sequestering substrates, ranging from proteins to aggregates and organelles, into autophagosomes for lysosomal degradation. In these processes cells need to coordinate between substrate remodeling and autophagosome formation for efficient engulfment. We found that in Parkin-mediated mitophagy, mitochondria to be turned over first become grape-like mitoaggregates, followed by their disassembly into smaller pieces via the actinomyosin system. At the disassembly step, we observed spatially-associated, synchronous formation of circular F-actin and BATS-labeled autophagy initiation sites near mitochondria, suggesting coordination between substrate downsizing and autophagosome formation during mitophagy. Interestingly, PtdIns(4,5)P2, instead of PtdIns(3)P, regulates this mitophagy-associated formation of circular F-actin and BATS-sites. Selective depletion of PtdIns(4,5)P2 near omegasomes, the endoplasmic reticulum (ER) subdomains involved in autophagosome formation, impaired mitoaggregate disassembly. Our findings demonstrate the presence of a pool of PtdIns(4,5)P2 adjacent to omegasomes, and that they coordinate mitoaggregate disassembly with autophagy initiation during Parkin-mediated mitophagy.