Invited Talk 21st International Conference on Biological Inorganic Chemistry 2025

Highly antitumor-active azolato-bridged dinuclear Pt(II) complexes induce DNA compaction and liquid-liquid phase separation. (122227)

Seiji Komeda 1 , Takuma Yamada 1 , Masako Uemura 1 , Ryu Tashiro 1 , Keiichi Hiramoto 1
  1. Suzuka University of Medical Science, Suzuka, MIE, Japan

The series of azolato-bridged dinuclear platinum(II) complexes [{cis-Pt(NH3)2}2(μ-OH)(μ-azolato]2+ (azolato-bridged complexes) are known to be highly effective on cancers both in vitro and in vivo.[1,2] The purpose of our research is to develop next-generation platinum-based drugs and molecular tools that can control the higher-order structure of DNA by focusing on its unique DNA binding mode. More than twenty azolato-bridged complexes were synthesized, and some derivatives exhibited much higher in vivo antitumor efficacy than oxaliplatin against mouse homografted Colon-26 colorectal tumor. Especially, one of the derivatives exhibited markedly high and long-lasting therapeutic effect even against large-sized tumors, and experiments with immunodeficient tumor-bearing mice suggest that the complex has immunostimulatory activity. Apart from the development of anticancer drugs, microscopic observations revealed that these complexes significantly change the higher-order structure of double-stranded DNA[3,4]  and induce liquid-liquid phase separation in single-stranded DNA solutions. Various application studies based on azolato-bridged complexes will be presented.

  1. Komeda, S. et al., Metallomics (2013) 5, 461-8.
  2. Uemura, M. et al., Inorg. Chem. (2022) 61, 12155-64.
  3. Komeda, S. et al., Inorg. Chem. (2017) 56, 802-11.
  4. Imai, R. et al., Sci. Rep. (2016) 6, 24712