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DNA Topoisomerases

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Topoisomerases are enzymes that relax overwound DNA molecules during various cell processes, including DNA replication and transcription. These enzymes regulate positive and negative DNA supercoiling without changing the nucleotide sequence. DNA overwinding in a clockwise direction results in positively supercoiled DNA, whereas underwinding in a counterclockwise direction produces negatively supercoiled DNA.
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Pyrazole-Infused Metal Complexes: Anticancer Activity, DNA Cleavage, and Biophysical Insights into DNA/BSA

Tankadhar Behera¹, Jyotiprabha Rout¹, Namita Bhoi²

¹School of Chemistry, Sambalpur University, Jyoti Vihar, Sambalpur, Odisha 768019, India.

ACS Applied Bio Materials

|September 17, 2025

Summary

This study synthesized and characterized novel pyrazole-based metal complexes (Co(II), Cu(II), Zn(II)) that effectively bind to DNA and proteins. Complex 2 demonstrates potent DNA cleavage activity, mediated by reactive oxygen species, and exhibits promising cytotoxic effects against breast cancer cells.

Keywords:

DNA cleavage X-ray crystallography anticancer activity biophysical interactions cytotoxicity electrophoresis metal complex pyrazole

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Area of Science:

Coordination Chemistry
Bioinorganic Chemistry
Chemical Biology

Background:

Pyrazole-based ligands are versatile building blocks in coordination chemistry.
Metal complexes can exhibit diverse biological activities, including DNA binding and cleavage.
Understanding structure-activity relationships is crucial for developing novel therapeutic agents.

Purpose of the Study:

To synthesize and characterize novel cobalt(II), copper(II), and zinc(II) complexes with a dimethylpyrazole ligand.
To investigate the DNA and protein binding capabilities of these complexes.
To evaluate their DNA cleavage activity, mechanism, and cytotoxicity against cancer cell lines.

Main Methods:

Synthesis and characterization of metal complexes using FTIR, UV-vis, ESI-HRMS, and X-ray diffraction.
Spectroscopic studies (UV-vis, fluorescence) for DNA and protein binding.
Gel electrophoresis for DNA cleavage assays, MTT assay for cytotoxicity, and flow cytometry for apoptosis analysis.

Main Results:

Successfully synthesized and characterized [CoCl2(dmp)2] (1), [CuCl2(dmp)2]2 (2), and [ZnCl2(dmp)2] (3) complexes.
Complexes 1-3 exhibit strong binding to bovine serum albumin and calf thymus DNA.
Complex 2 shows significant self-activating DNA cleavage, enhanced by ascorbate and H2O2, involving ROS.
Cytotoxicity assays reveal varying IC50 values against MCF-7, MDA-MB-231, and HEK-293 cell lines.
Apoptotic effects on MDA-MB-231 cells are primarily mediated through the late apoptotic pathway.

Conclusions:

The synthesized pyrazole-based metal complexes possess DNA binding and cleavage properties.
Complex 2 is a potent chemical nuclease, with its activity dependent on reactive oxygen species.
These complexes demonstrate potential as anticancer agents, inducing apoptosis in breast cancer cells.