Triazene salts: Design, synthesis, ctDNA interaction, lipophilicity determination, DFT calculation, and...

Area of Science:

• Medicinal Chemistry
• Organic Synthesis
• Cancer Biology

Background:

• Triazene compounds are explored for their potential anticancer properties.
• Developing novel agents with selective toxicity against cancer cells is a critical research area.

Purpose of the Study:

• To synthesize and characterize novel triazene salts.
• To evaluate the antiproliferative activity of these compounds against a panel of human cancer cell lines.
• To assess the selectivity of these compounds towards cancer cells compared to normal cells.

Main Methods:

• Synthesis of nine triazene salts.
• Structural elucidation using 1H and 13C NMR, and GC-APCI-MS.
• In vitro antiproliferative assays against human cancer cell lines (MV-4-11, MCF-7, JURKAT, HT-29, Hep-G2, HeLa, Du-145, DAUDI) and a normal cell line (MCF-10A).
• Lipophilicity determination using reversed-phase ultra-performance liquid chromatography.
• UV-Vis spectroscopy to investigate DNA interaction.
• Theoretical calculations (Density Functional Theory) for 1H NMR shifts.

Main Results:

• Compounds 2c, 2d, 2e, and 2f exhibited potent antiproliferative activity against MV4-11 cells (IC50: 5.42–7.69 µg/mL).
• These active compounds showed 6-11 times lower cytotoxicity against normal MCF-10A cells.
• Compounds 2c and 2f were highly effective against DAUDI and HT-29 cells (IC50: 4.91 µg/mL and 5.59 µg/mL, respectively).
• Lipophilicity correlated with antiproliferative effects, and UV-Vis data suggested DNA interaction.

Conclusions:

• Novel triazene salts possess significant antiproliferative activity against specific human cancer cell lines.
• Compounds 2c-2f demonstrate promising selective cytotoxicity, warranting further investigation as potential anticancer agents.
• The study provides insights into the structure-activity relationship and potential DNA-binding mechanism of these triazene salts.