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

Abstract

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 × 103 M−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.