Triazole-based, optically-pure metallosupramolecules; highly potent and selective anticancer compounds

Area of Science:

• Coordination Chemistry
• Supramolecular Chemistry
• Medicinal Chemistry

Background:

• Triazole aldehydes are versatile building blocks in supramolecular chemistry.
• Metallohelices offer unique structural and functional properties for various applications.
• Developing selective anticancer agents is a critical challenge in medicine.

Purpose of the Study:

• To synthesize and characterize novel functionalised triazole aldehydes.
• To investigate the self-assembly of these aldehydes into metallohelices with iron(II) and zinc(II).
• To evaluate the antiproliferative activity and selectivity of the resulting metallohelices against cancer cell lines.

Main Methods:

• Synthesis of functionalised triazole aldehydes.
• Coordination-driven self-assembly with Fe(II) and Zn(II) salts.
• Characterization of metallohelices using spectroscopy and X-ray crystallography.
• In vitro antiproliferative assays against a panel of cancerous and non-cancerous cell lines.

Main Results:

• Highly selective self-assembly yielded water-compatible, optically pure, low-symmetry Fe(II)- and Zn(II)-based metallohelices.
• Sub-micromolar antiproliferative activity was observed against various human cancer cell lines.
• Excellent selectivity was demonstrated against non-cancerous cell lines, indicating a favorable therapeutic window.
• Potential for synergistic combinatorial therapy with cisplatin was identified.

Conclusions:

• Functionalised triazole aldehydes are effective precursors for constructing sophisticated metallohelical architectures.
• The developed metallohelices exhibit potent and selective anticancer properties.
• These findings highlight the potential of metallohelices in targeted cancer therapy and drug development.