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First paraben substituted cyclotetraphosphazene compounds and DNA interaction analysis with a new automated biosensor
Gönül Yenilmez Çiftçi1, Elif Şenkuytu1, Saadet Elif İncir1
1Department of Chemistry, Gebze Technical University, 41400 Gebze, Kocaeli, Turkey.
Abstract:
Cancer, as one of the leading causes of death in the world, is caused by malignant cell division and growth that depends on rapid DNA replication. To develop anti-cancer drugs this feature of cancer could be exploited by utilizing DNA-damaging molecules. To achieve this, the paraben substituted cyclotetraphosphazene compounds have been synthesized for the first time and their effect on DNA (genotoxicity) has been investigated. The conventional genotoxicity testing methods are laborious, take time and are expensive. Biosensor based assays provide an alternative to investigate this drug/compound DNA interactions. Here for the first time, a new, easy and rapid screening method has been used to investigate the DNA damage, which is based on an automated biosensor device that relies on the real-time electrochemical profiling (REP™) technology. Using both the biosensor based screening method and the in vitro biological assay, the compounds 9 and 11 (propyl and benzyl substituted cyclotetraphosphazene compounds, respectively), have resulted in higher DNA damage than the others with 65% and 80% activity reduction, respectively.
Insights
New cyclotetraphosphazene compounds show potential as anti-cancer agents by damaging cancer cell DNA. A novel biosensor screening method rapidly identified compounds with significant genotoxicity, offering a faster alternative to traditional testing.
Area of Science:
- Medicinal Chemistry
- Genotoxicology
- Biosensor Technology
Background:
- Cancer is a leading cause of death, characterized by uncontrolled cell division reliant on DNA replication.
- Developing novel anti-cancer drugs often involves targeting DNA replication with damaging molecules.
- Traditional genotoxicity testing is time-consuming, labor-intensive, and costly.
Purpose of the Study:
- To synthesize novel paraben-substituted cyclotetraphosphazene compounds for the first time.
- To investigate the genotoxic effects of these synthesized compounds on DNA.
- To establish a rapid and efficient screening method for assessing DNA damage using biosensor technology.
Main Methods:
- Synthesis of novel paraben-substituted cyclotetraphosphazene compounds.
- Application of a new, automated biosensor device utilizing real-time electrochemical profiling (REP™) technology for DNA damage assessment.
- Validation of biosensor findings using in vitro biological assays.
Main Results:
- Compounds 9 (propyl-substituted) and 11 (benzyl-substituted) cyclotetraphosphazenes exhibited significant DNA damaging activity.
- Compound 9 demonstrated 65% activity reduction, while Compound 11 showed 80% activity reduction.
- The biosensor-based screening method proved effective for rapid genotoxicity evaluation.
Conclusions:
- Paraben-substituted cyclotetraphosphazene compounds represent a promising class of potential anti-cancer agents.
- Compounds 9 and 11 are particularly effective DNA-damaging agents among the synthesized series.
- The REP™-based biosensor assay offers a viable, rapid, and cost-effective alternative for genotoxicity screening.
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