👤 Lan YX

Title: A Bioactive Benzimidazole-Cyclometalated Iridium(III) Complex as an Epigenetic Regulator through Effectively Interrupting the EED-EZH2 Interaction. Abstract: Epigenetic regulation plays a fundamental role in controlling gene expression and maintaining cellular identity. Among epigenetic processes, the translocation of methyltransferases is critical for the modification of chromatin structure and transcriptional activity. The regulation of these translocation events and the mechanisms involved are complex, yet critical for understanding and manipulating epigenetic states. Therefore, novel strategies are required for detecting and visualizing the movement and interaction of methyltransferases within cells. Using enhancer of zeste homolog 2 (EZH2) methyltransferase as an example, a bifunctional compound capable of both monitoring and disrupting its translocation process is developed by targeting the protein-protein interaction (PPI) between embryonic ectoderm development (EED) and EZH2. The Ir(III) complex 1 bound enthalpically to EED and effectively inhibited the methyltransferase activity of EZH2. Moreover, disruption of the EED-EZH2 PPI led to increased transcriptional activity of P21 and P27, resulting in the suppression of triple-negative breast cancer (TNBC) cell proliferation. Excitingly, 1 suppressed tumor metastasis in a TNBC mouse model in vivo. To our knowledge, complex 1 is the first metal-based bifunctional therapeutic agent designed to probe and inhibit the EED-EZH2 PPI, highlighting the feasibility and significance of using metal complexes to monitor and influence methyltransferase translocations for therapeutic applications. Show less

Photodynamic therapy (PDT) using two-photon near-infrared light excitation is a very effective way to avoid the use of short-wavelength ultraviolet or visible light which cannot efficiently penetrate into the biological tissues and is harmful to the healthy cells. Herein, a series of cyclometalated Ir(III) complexes with a structurally simple diimine ligand were designed and the synthetic route and preparation procedure were optimized, so that the complexes could be obtained in apparently higher yield, productivity, and efficiency in comparison to the traditional methods. Their ground state and excited singlet and triplet state properties were studied by spectroscopy and quantum chemistry theoretical calculations to investigate the effect of substituent groups on the photophysical properties of the complexes. The Ir(III) complexes, especially Ir1 and Ir3, showed very low dark toxicities and high phototoxicities under both one-photon and two-photon excitation, indicating their great potential as PDT agents. They were also found to be highly sensitive two-photon mitochondria dyes. Show less

A new Ru(II) complex [Ru(dmp)2(NMIP)](ClO4)2 (dmp = 2,9-dimethyl-1,10-phenanthroline, NMIP = 2'-(2″-nitro-3″,4″-methylenedioxyphenyl)imidazo[4',5'-f][1,10]-phenanthroline) was synthesized and characterized by elemental analysis, ESI-MS and (1)H NMR. The cytotoxic activity of the complex against MG-63, U2OS, HOS, and MC3T3-e1 cell lines was investigated by MTT method. The complex shows moderate cytotoxicity toward HOS (IC50 = 35.6 ± 2.6 µM) and MC3T3-e1 (IC50 = 41.6 ± 2.8 µM) cell lines. The morphological studies show that the complex can induce apoptosis in HOS cells and cause an increase of reactive oxygen species levels and a decrease in the mitochondrial membrane potential. The cell cycle distribution demonstrates that the complex inhibits the cell growth at S phase. Additionally, the antitumor activity in vivo reveals that the complex can induce a decrease in tumor weight. Show less