Cargando…

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 ac...

Descripción completa

Detalles Bibliográficos
Autores principales: Mehran, Shiva, Rasmi, Yousef, Karamdel, Hamid Reza, Hossinzadeh, Ramin, Gholinejad, Zafar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949734/
https://www.ncbi.nlm.nih.gov/pubmed/31975999
http://dx.doi.org/10.1155/2019/4936351
Descripción
Sumario: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 × 10(3) 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.