In vitro cytotoxicity and DNA/HSA interaction study of triamterene using molecular modelling and multi-spectroscopic...

Area of Science:

• Pharmacology and Molecular Biology
• Biochemistry

Background:

• Triamterene's potential anticancer activity warrants investigation.
• Understanding drug-DNA and drug-protein interactions is crucial for drug development.

Purpose of the Study:

• To evaluate the in vitro anticancer activity of triamterene against colon cancer cell lines.
• To elucidate the mechanism of triamterene's interaction with calf thymus DNA (ct-DNA) and human serum albumin (HSA).

Main Methods:

• In vitro cytotoxicity assays (MTT) were performed on HCT116 and CT26 cells.
• Spectroscopic techniques (UV-Vis, fluorescence) and viscosity measurements were used to study drug-DNA interactions.
• Competitive binding studies with HSA and molecular docking were employed to understand drug-protein and drug-DNA binding modes.

Main Results:

• Triamterene demonstrated significant in vitro anticancer activity with IC50 values of 31.30 μM (HCT116) and 24.45 μM (CT26).
• Viscosity data and competitive studies with intercalator probes (NR, MB) confirmed intercalation as the DNA binding mode.
• Triamterene competes with warfarin for site I on HSA, indicating a specific binding interaction.

Conclusions:

• Triamterene possesses promising anticancer properties against colon cancer cells.
• The drug interacts with DNA via intercalation and with HSA through competitive binding at site I.
• These findings provide insights into triamterene's mechanism of action and potential therapeutic applications.