Comprehensive Multi-Spectroscopic Characterization and Molecular Docking Investigation of the Interaction Between the Anticancer Agent Heptaplatin and ct-DNA


Bozaslan M. Ş., Toksoy S. C., Özkul M. A., Akgül T., DİKMEN G.

ChemistrySelect, cilt.10, sa.42, 2025 (SCI-Expanded, Scopus) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 10 Sayı: 42
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1002/slct.202504089
  • Dergi Adı: ChemistrySelect
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core
  • Anahtar Kelimeler: ct-DNA, DNA binding, Heptaplatin, Spectroscopic methods
  • Eskişehir Osmangazi Üniversitesi Adresli: Evet

Özet

Molecular interactions between DNA and low-molecular-weight compounds are crucial in pharmaceutical research, as DNA is a primary cellular target for many anticancer agents. Heptaplatin (HTP), a platinum-based drug, exhibits stronger and broader anticancer activity than other platinum derivatives. While DNA binding studies with cisplatin and oxaliplatin are well established, limited information exists on HTP–DNA interactions. In this study, UV-Vis and fluorescence spectroscopy were used to elucidate the binding mechanism between calf thymus DNA (ct-DNA) and HTP. Increasing ct-DNA concentration led to a significant decrease in HTP fluorescence intensity, yielding a quenching constant of 8.82 × 1013 M−1. Binding constants (Kb) were 1.97 × 10⁴ M−1 from UV-Vis and 1.17 × 10⁴ M−1 from fluorescence data. Competitive binding assays with ethidium bromide and Hoechst 33258 indicated a groove-binding mode. Viscosity and thermal denaturation experiments supported this interaction model. Negative enthalpy (ΔH°) and entropy (ΔS°) values revealed that van der Waals forces and hydrogen bonding stabilize the HTP–DNA complex. Additionally, the decrease in the Stern–Volmer quenching constant with temperature confirmed static quenching. Molecular docking simulations further verified that HTP preferentially binds within the DNA minor groove via hydrogen bonding and van der Waals interactions.