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All ortho–para directors, excluding halogens, are activating groups. These groups donate electrons to the ring, making the ring carbons electron-rich. Consequently, the reactivity of the aromatic ring towards electrophilic substitution increases. For instance, the nitration of anisole is about 10,000 times faster than the nitration of benzene. The electron-donating effect of the methoxy group in anisole activates the ortho and para positions on the ring and stabilizes the corresponding...
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During the electron transport chain, electrons from NADH and FADH2 are first transferred to complexes I and II, respectively. These two complexes then transfer the electrons to ubiquinol, which carries them further to complex III. Complex III passes the electrons across the intermembrane space to Cyt c, which carries them further to complex IV. Complex IV donates electrons to oxygen and reduces it to water. As electrons pass through complexes I, III, and IV, the energy released aids the pumping...
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Crystal Field Theory
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Developing a binuclear multi-target Bi(III) complex by optimizing 2-acetyl-3-ethylpyrazine thiosemicarbazides.

Muhammad Hamid Khan1, Meiling Cai1, Shanhe Li1

  • 1State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Ministry of Science and Technology of China, Guangxi Normal University, Guilin, Guangxi, China.

European Journal of Medicinal Chemistry
|August 20, 2019
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Summary

Novel bismuth (Bi) complexes show promise as multi-target anticancer agents. A lead compound, C4, effectively inhibited human bladder cancer cell proliferation, cell cycle progression, and metastasis.

Keywords:
Anti-metastatic activityAnticancer activityBi(III) complexMulti-targeting mechanism

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Area of Science:

  • Medicinal Chemistry
  • Oncology
  • Materials Science

Background:

  • Single-target anticancer metal agents have limitations.
  • Bismuth (Bi) complexes offer antiproliferative activity with minimal side effects.
  • Multi-target agents are a promising strategy for cancer therapy.

Purpose of the Study:

  • To design and synthesize novel binuclear Bi(III) complexes.
  • To investigate structure-activity relationships of these complexes against human cancer cell lines.
  • To identify a lead Bi drug candidate for bladder cancer treatment.

Main Methods:

  • Synthesis of four novel binuclear Bi(III) complexes based on modified thiosemicarbazides.
  • Evaluation of antiproliferative activity against human cancer cell lines.
  • Cell cycle analysis, apoptosis and autophagy pathway investigation, and metastasis inhibition assays.

Main Results:

  • A lead Bi drug, C4, demonstrated significant antiproliferative activity against T24 human bladder cancer cells.
  • C4 induced S-phase cell cycle arrest by regulating cyclin and cyclin-dependent kinases.
  • C4 activated apoptotic and autophagic signaling pathways and inhibited cell metastasis.

Conclusions:

  • The novel binuclear Bi(III) complex C4 exhibits multi-target anticancer properties.
  • C4 shows potential as a lead compound for developing next-generation anticancer metal agents.
  • The study highlights the therapeutic potential of bismuth complexes in cancer treatment.