New Iminodiacetate-Thiosemicarbazone Hybrids and Their Copper(II) Complexes Are Potential Ribonucleotide Reductase R2...

Area of Science:

• Medicinal Chemistry
• Biochemistry
• Cancer Biology

Background:

• Ribonucleotide reductase (RNR) is vital for nucleic acid synthesis and a key target in anticancer drug development.
• Thiosemicarbazones, like Triapine, are known RNR inhibitors that function by chelating transition metals.

Purpose of the Study:

• To synthesize and characterize novel iminodiacetate-thiosemicarbazone ligands and their dicopper(II) complexes.
• To evaluate the antiproliferative activity and selectivity of these compounds against various cancer cell lines.
• To investigate the mechanism of action of lead compounds as RNR inhibitors.

Main Methods:

• Synthesis and full characterization of six thiosemicarbazone ligands and six dicopper(II) complexes using analytical, spectroscopic (IR, UV-vis, NMR), mass spectrometry, and X-ray diffraction.
• Assessment of antiproliferative effects on human cancer and noncancerous cell lines.
• In vitro studies including molecular docking, microscale thermophoresis, electron paramagnetic resonance, and UV-vis spectroscopy to analyze RNR inhibition.

Main Results:

• Several synthesized thiosemicarbazones and their copper(II) complexes exhibited significant cytotoxicity and selectivity towards cancer cells.
• Molecular docking identified promising lead compounds for further investigation.
• In vitro analyses confirmed the interaction of lead compounds with RNR and their effect on the Fe(III)2-Y· cofactor.

Conclusions:

• The novel thiosemicarbazone derivatives and their dicopper(II) complexes are effective antiproliferative agents against cancer cell lines.
• These compounds target RNR, highlighting their potential as anticancer drug candidates.
• Further investigation is warranted to explore their therapeutic potential in cancer treatment.