Dataset Information

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.

SUBMITTER: Mehran S

PROVIDER: S-EPMC6949734 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Mehran Shiva S Rasmi Yousef Y Karamdel Hamid Reza HR Hossinzadeh Ramin R Gholinejad Zafar Z

Evidence-based complementary and alternative medicine : eCAM 20191224

<h4>Introduction</h4>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.<h4>Methods</h4>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 a ...[more]

PMID: 31975999

Similar Datasets

Project description:DNA binding investigations are critical for designing better pharmaceutical compounds since the binding of a compound to dsDNA in the minor groove is critical in drug discovery. Although only one in vitro study on the DNA binding mode of apigenin (APG) has been conducted, there have been no electrochemical and theoretical studies reported. We hereby report the mechanism of binding interaction of APG and a new class of sulfonamide-modified flavonoids, apigenin disulfonamide (ADSAM) and apigenin trisulfonamide (ATSAM), with deoxyribonucleic acid (DNA). This study was conducted using multispectroscopic instrumentation techniques, which include UV-vis absorption, thermal denaturation, fluorescence, and Fourier transform infrared (FTIR) spectroscopy, and electrochemical and viscosity measurement methods. Also, molecular docking studies were conducted at room temperature under physiological conditions (pH 7.4). The molecular docking studies showed that, in all cases, the lowest energy docking poses bind to the minor groove of DNA and the apigenin-DNA complex was stabilized by several hydrogen bonds. Also, ?-sulfur interactions played a role in the stabilization of the ADSAM-DNA and ATSAM-DNA complexes. The binding affinities of the lowest energy docking pose (schematic diagram of table of content (TOC)) of APG-DNA, ADSAM-DNA, and ATSAM-DNA complexes were found to be -8.2, -8.5, and -8.4 kcal mol-1, respectively. The electrochemical binding constants K b were determined to be (1.05 × 105) ± 0.04, (0.47 × 105) ± 0.02, and (8.13 × 105) ± 0.03 for APG, ADSAM, and ATSAM, respectively (all of the tests were run in triplicate and expressed as the mean and standard deviation (SD)). The K b constants calculated for APG, ADSAM, and ATSAM are in harmony for all techniques. As a result of the incorporation of dimethylsulfamate groups into the APG structure, in the ADSAM-dsDNA and ATSAM-dsDNA complexes, in addition to hydrogen bonds, ?-sulfur interactions have also contributed to the stabilization of the ligand-DNA complexes. This work provides new insights that could lead to the development of prospective drugs and vaccines.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure