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Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents
Published on: May 28, 2014
A novel candidate compound with urethane structure for anticancer drug development
Atsuko Matsuoka1, Kazuo Isama, Susumu Tanimura
1Division of Medical Devices, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan. matsuoka@nihs.go.jp
Current Drug Discovery Technologies
|August 19, 2007
Summary
Diethyl-4,4'-methylenebis(N-phenylcarbamate) (MDU) is a potent anticancer agent that inhibits tubulin polymerization. This urethane compound demonstrates strong cytotoxicity and induces chromosome aberrations, offering a promising, stable, and inexpensive new drug candidate.
Area of Science:
- Chemical Synthesis and Pharmacology
- Cancer Research
- Cell Biology
Background:
- Polyurethane hydrolysis investigation led to the synthesis of novel urethane compounds.
- Diethyl-4,4'-methylenebis(N-phenylcarbamate) (MDU) was among four compounds synthesized for hydrolysis studies.
- Initial research focused on understanding polyurethane degradation pathways.
Purpose of the Study:
- To evaluate the cytotoxicity of MDU and related compounds in various cell lines.
- To investigate MDU's potential to induce chromosomal damage, including aberrations and micronuclei.
- To explore MDU's mechanism of action, specifically its potential as a tubulin inhibitor.
Main Methods:
- Cytotoxicity assays were performed on Chinese hamster (CHL, V79) and human (HeLa S3) cancer cell lines.
- Chromosome aberration (CA) and micronucleus (MN) tests were conducted on CHL cells.
- COMPARE analysis and tubulin polymerization assays were used to determine MDU's mechanism of action.
Main Results:
- MDU exhibited the highest cytotoxicity with an IC50 of approximately 0.1 microg/ml across all tested cell lines.
- MDU induced significant polyploidy, chromosome aberrations, and micronuclei formation in CHL cells.
- MDU demonstrated superior mitotic arrest induction compared to taxol and colchicine and inhibited tubulin polymerization.
Conclusions:
- MDU is a potent cytotoxic agent with significant genotoxic effects, suggesting potential as an anticancer drug.
- MDU functions as a tubulin polymerization inhibitor, similar to established anticancer agents.
- MDU presents a promising profile as a novel, stable, room-temperature-stable, and cost-effective anticancer therapeutic.
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