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Published on: February 9, 2021
Synthesis of Dihydrazones as Potential Anticancer and DNA Binding Candidates: A Validation by Molecular Docking
Malavalli B Sridhara1, Kadalipura P Rakesh2, Honnayakanahalli M Manukumar3
1Department of Chemistry, Rani Channamma University, Vidyasangama, Belagavi-591156, Karnataka, India.
Background:
Accounting for mortality nearly one in four of human and second highest leading cause of death worldwide. Every year, about 10 million new cancers are diagnosed and causing major health issues in both developing and developed countries.
Methods:
A series of new dihydrazones were synthesized and screened for in vitro anticancer activity against three different MDA-MB-231, A546 and MCF7 cell lines and validated by DNA binding and molecular docking approaches.
Result:
In the present investigations, synthesized compounds 21, 22, 23 and 24 exhibited potent anticancer activity against tested cancer cell lines and DNA binding study using methyl green comparing to Doxorubicin and ethidium bromide as a positive control respectively.
Conclusion:
The Structure Activity Relationship (SAR) showed that the electron withdrawing groups (-Cl, -NO2, - F, and -Br) favored the DNA binding studies and anticancer activity whereas, electron donating groups (-OH and - OCH3) showed moderate activity. In the molecular docking study, binding interactions of the most active compounds 21, 22, 23 and 24 stacked with A-T rich regions of the DNA minor groove by surface binding interactions were confirmed. Further, the tuning of active analogs for targeted therapy was warranted.
Insights
New dihydrazone compounds show potent anticancer activity by binding to DNA. Structure-activity relationships reveal electron-withdrawing groups enhance efficacy, suggesting potential for targeted cancer therapies.
Area of Science:
- Medicinal Chemistry
- Molecular Biology
- Drug Discovery
Background:
- Cancer is a leading global cause of mortality, with millions of new cases diagnosed annually.
- It presents significant health challenges in both developing and developed nations worldwide.
Purpose of the Study:
- To synthesize and evaluate novel dihydrazone compounds for anticancer properties.
- To investigate the mechanism of action through DNA binding and molecular docking studies.
Main Methods:
- Synthesis of a series of new dihydrazone compounds.
- In vitro screening against MDA-MB-231, A546, and MCF7 cancer cell lines.
- DNA binding assays using methyl green and molecular docking simulations.
Main Results:
- Compounds 21, 22, 23, and 24 demonstrated significant in vitro anticancer activity.
- DNA binding studies confirmed interactions, with electron-withdrawing groups enhancing activity.
- Molecular docking revealed compounds binding to A-T rich DNA regions.
Conclusions:
- The synthesized dihydrazones exhibit promising anticancer potential.
- Structure-activity relationship analysis guides further optimization for targeted cancer therapy.
- These findings warrant further investigation into active analogs for therapeutic development.
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