More Like this

1. In‐vitro and In‐vivo Photocatalytic Cancer Therapy with Biocompatible Iridium(III) Photocatalysts

   https://doi.org/10.1002/anie.202015671  

   Huang, Can ; Liang, Chao ; Sadhukhan, Tumpa ; Banerjee, Samya ; Fan, Zhongxian ; Li, Tingxuan ; Zhu, Zilin ; Zhang, Pingyu ; Raghavachari, Krishnan ; Huang, Huaiyi ( March 2021 , Angewandte Chemie International Edition)

   Photocatalytic anticancer profile of a Ir^IIIphotocatalyst (Ir3) with strong light absorption, high turnover frequency, and excellent biocompatibility is reported.Ir3showed selective photo‐cytotoxicity against cisplatin‐ and sorafenib‐resistant cell lines while remaining dormant to normal cell lines in the dark.Ir3exhibited excellent photo‐catalytic oxidation of cellular co‐enzyme, the reduced nicotinamide adenine dinucleotide phosphate (NADPH), and amino acids via a single electron transfer mechanism. The photo‐induced intracellular redox imbalance and change in mitochondrial membrane potential resulted in necrosis and apoptosis of cancer cells. Importantly,Ir3exhibited high biocompatibility and photo‐catalytic anticancer efficiency as evident from in vivo zebrafish and mouse cancer models. To the best of our knowledge,Ir3is the first Ir^IIIbased photocatalyst with such a high biocompatibility and photocatalytic anticancer therapeutic effect.

    

   more » « less
2. Novel histone deacetylase inhibitors bearing a 4‐piperidin‐4‐yl‐triazole scaffold as antitumor agents

   https://doi.org/10.1002/ddr.21603  

   Wang, Yan ; Su, Li ; Wang, Qiang ; Zhang, Li ; Luan, Yepeng ( October 2019 , Drug Development Research)

   Histone deacetylases have proven to be promising targets for the development of anticancer drugs. In this work, we reported the design and synthesis of a series of 20 novel hydroxamic acid‐based histone deacetylase inhibitors with 4‐piperidin‐4‐yl‐triazole as the core structure. Five newly obtained compounds displayed excellent HDAC6 inhibitory activities. Among them, compounds WY‐12 and WY‐15 also exhibited excellent antiproliferative activities against six human tumor cell lines. WY‐15 could increase the level of acetylated histone H3 in a dose‐dependent manner. Furthermore, WY‐15 remarkably induced cell cycle arrest of Sy5y cancer cells in G₀/G₁phase. Finally, the high potency of compound WY‐15 toward HDAC6 was rationalized by molecular docking study.

    

   more » « less
3. Deciphering the mechanism of the Ni-photocatalyzed C‒O cross-coupling reaction using a tridentate pyridinophane ligand

   https://doi.org/10.1038/s41467-022-28948-8  

   Na, Hanah ; Mirica, Liviu M. ( March 2022 , Nature Communications)

   Photoredox nickel catalysis has emerged as a powerful strategy for cross-coupling reactions. Although the involvement of paramagnetic Ni(I)/Ni(III) species as active intermediates in the catalytic cycle has been proposed, a thorough spectroscopic investigation of these species is lacking. Herein, we report the tridentate pyridinophane ligands^RN3 that allow for detailed mechanistic studies of the photocatalytic C–O coupling reaction. The derived (^RN3)Ni complexes are active catalysts under mild conditions and without an additional photocatalyst. We also provide direct evidence for the key steps involving paramagnetic Ni species in the proposed catalytic cycle: the oxidative addition of an aryl halide to a Ni(I) species, the ligand exchange/transmetalation at a Ni(III) center, and the C–O reductive elimination from a Ni(III) species. Overall, the present work suggests the^RN3 ligands are a practical platform for mechanistic studies of Ni-catalyzed reactions and for the development of new catalytic applications.

    

   more » « less
4. Anticancer polymers designed for killing dormant prostate cancer cells

   https://doi.org/10.1038/s41598-018-36608-5  

   Takahashi, Haruko ; Yumoto, Kenji ; Yasuhara, Kazuma ; Nadres, Enrico T. ; Kikuchi, Yutaka ; Buttitta, Laura ; Taichman, Russell S. ; Kuroda, Kenichi ( January 2019 , Scientific Reports)

   The discovery of anticancer therapeutics effective in eliminating dormant cells is a significant challenge in cancer biology. Here, we describe new synthetic polymer-based anticancer agents that mimic the mode of action of anticancer peptides. These anticancer polymers developed here are designed to capture the cationic, amphiphilic traits of anticancer peptides. The anticancer polymers are designed to target anionic lipids exposed on the cancer cell surfaces and act by disrupting the cancer cell membranes. Because the polymer mechanism is not dependent on cell proliferation, we hypothesized that the polymers were active against dormant cancer cells. The polymers exhibited cytotoxicity to proliferating prostate cancer. Importantly, the polymer killed dormant prostate cancer cells that were resistant to docetaxel. This study demonstrates a new approach to discover novel anticancer therapeutics.

    

   more » « less
5. New Isoxazole‐Substituted Aryl Iodides: Metal‐Free Synthesis, Characterization and Catalytic Activity

   https://doi.org/10.1002/ejoc.202301191  

   Rimi ; Uttam, Bhawna ; Zhdankin, Viktor V. ; Kumar, Ravi ( February 2024 , European Journal of Organic Chemistry)

   A series of new isoxazole‐substituted aryl iodides1 a–1 dhave been synthesized by DIB‐mediated [3+2] cycloaddition reaction of 2‐iodo‐1,3‐bis(prop‐2‐yn‐1‐yloxy) benzene (4) with corresponding benzaldehyde oximes5 a–5 d. Structure of the synthesized aryl iodides1were characterized by IR,¹H NMR,¹³C NMR and HRMS. The structure of1 awas also confirmed by single‐crystal X‐ray crystallography. Further, catalytic activity of iodoarenes1 a–1 dwas screened for the oxidation of hydroquinones and sulfides. On oxidation using aryl iodides1withm‐CPBA as terminal oxidant, hydroquinones afforded benzoquinones while sulfides gave corresponding sulfoxides in good to excellent yields. Iodoarene1 bshowed the best catalytic activity for the oxidation of sulfides and hydroquinones. Moreover, iodoarene1 b, was also utilized for α‐oxytosylation of acetophenones.

    

   more » « less