Synthesis, Characterization, DNA Interactions, Cleavage, Cytotoxic Evaluation and Molecular Modeling Studies of of Tin–Based Cancer Chemotherapy Drug as Topoisomerase I Inhibitor

EasyChair Preprint 9339

Abstract

The new organotin complex 1 derived from propyl gallate and 1,10–phenanthroline was designed, synthesized and characterized by spectroscopic (IR, UV–vis, ESI–MS and (1H, 13C, 119Sn) NMR and elemental analytical methods. the underlying mechanisms of the anticancer action of complex 1 was further elucidated by evaluating its in vitro DNA interaction studies of complex 1 with calf thymus DNA and the regulating signaling pathways. The in vitro DNA binding studies of 1 with calf thymus DNA in Tris–HCl buffer was studied by various biophysical methods (Uv/Vis, Fluorescence, and circular dichroism) which reveal that complex 1 bind to CT DNA non–covalently via electrostatic interaction. The higher Kb value of complex 1 suggested greater DNA binding propensity. The complex 1 exhibits DNA cleavage activity with supercoiled pBR322 in the presence of different activators. The complex cleaves DNA efficiently involving oxidative cleavage pathway. Molecular docking studies were performed to understand the binding mode of complex 1 with CT–DNA (PDB ID: 1BNA).

Keyphrases: DNA, Studies, binding

@booklet{EasyChair:9339,
  author    = {Waddhaah Mohammed Abdulgaleel Al-Asbahy and Mfeed K. A. Hassan and Manal Mohammed},
  title     = {Synthesis, Characterization, DNA Interactions, Cleavage, Cytotoxic Evaluation and Molecular Modeling Studies of of Tin–Based Cancer Chemotherapy Drug as Topoisomerase I Inhibitor},
  howpublished = {EasyChair Preprint 9339},
  year      = {EasyChair, 2022}}