In Vitro and In Silico DNA Binding Studies of Novel 1,2,3‐Triazole‐Based Coumarin Compounds

Coumarin-1,2,3-triazole hybrids represent a class of compounds with significant potential in medicinal chemistry due to their versatile biological activities. In this study, a series of novel coumarin-triazole derivatives was synthesized via Cu(I)-catalyzed azide-alkyne cycloaddition. The compounds were characterized by FT-IR, ¹H/¹ ³C NMR spectroscopy, and elemental analysis. Single-crystal x-ray analysis of compound 6 revealed a monoclinic crystal system stabilized by weak intramolecular C─H···O hydrogen bonds and π─π stacking interactions. DNA-binding studies, including UV-vis titration, fluorescence spectroscopy, and viscosity measurements, indicated predominant minor groove binding, with compound 6 showing the highest affinity (Kb = 6.19 × 10⁴ M⁻ ¹) and favorable thermodynamic parameters. Molecular docking of compound 6 demonstrated strong binding interactions with DNA, consistent with experimental results. ADME predictions for compound 6 indicated good oral bioavailability, low toxicity, and favorable pharmacokinetic properties. These findings highlight compound 6 as a promising drug-like candidate for further biological evaluation.