Study of the Binding Interaction between Wortmannin and Calf Thymus DNA: Multispectroscopic and Molecular Docking Studies

Introduction. Wortmannin (WTN) is a steroid metabolite that inhibits phosphatidylinositol 3-kinase and other signaling
pathways. Structurally, the WTN consists of a cyclopentanophenanthrene-like structure with several oxygen-rich moieties which
have the potential to interact with deoxyribonucleic acid (DNA) molecules. Methods. We aim to evaluate the WTN and calf
thymus DNA (ct-DNA) interaction with molecular docking using the AutoDock 4.2 software. UV and fluorescence spectroscopy
and viscosity techniques were performed to confirm the in silico analysis. Results. Molecular docking showed that the WTN
interacted with ct-DNA via hydrogen bonds at guanine-rich sequences. The number of hydrogen bonds between the WTN and
DNA was 1-2 bonds (average 1.2) per WTN molecule. The in silico binding constant was 2 ×103M− 1. UV spectroscopy showed
that the WTN induced a hyperchromic feature without wavelength shifting. The WTN and DNA interaction led to quenching of
DNA-emitted fluorescence. The different concentrations of WTN had no effect on DNA viscosity. Taken together, our results
demonstrated WTN interacts with DNA in the nonintercalating mode, which is considered as a new mechanism of action.
Conclusion. These results suggest that the WTN may exert its biological effects, at least in part, via interaction with DNA.