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Multi-spectroscopic, thermodynamic, and molecular docking/dynamic approaches for characterization of the binding interaction between calf thymus DNA and palbociclib

Studying the binding interaction between biological macromolecules and small molecules has formed the core of different research aspects. The interaction of palbociclib with calf thymus DNA at simulated physiological conditions (pH 7.4) was studied using different approaches, including spectrophotom...

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Autores principales: Magdy, Galal, Shaldam, Moataz A., Belal, Fathalla, Elmansi, Heba
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9427788/
https://www.ncbi.nlm.nih.gov/pubmed/36042232
http://dx.doi.org/10.1038/s41598-022-19015-9
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author Magdy, Galal
Shaldam, Moataz A.
Belal, Fathalla
Elmansi, Heba
author_facet Magdy, Galal
Shaldam, Moataz A.
Belal, Fathalla
Elmansi, Heba
author_sort Magdy, Galal
collection PubMed
description Studying the binding interaction between biological macromolecules and small molecules has formed the core of different research aspects. The interaction of palbociclib with calf thymus DNA at simulated physiological conditions (pH 7.4) was studied using different approaches, including spectrophotometry, spectrofluorimetry, FT-IR spectroscopy, viscosity measurements, ionic strength measurements, thermodynamic, molecular dynamic simulation, and docking studies. The obtained findings showed an apparent binding interaction between palbociclib and calf thymus DNA. Groove binding mode was confirmed from the findings of competitive binding studies with ethidium bromide or rhodamine B, UV–Vis spectrophotometry, and viscosity assessment. The binding constant (K(b)) at 298 K calculated from the Benesi–Hildebrand equation was found to be 6.42 × 10(3) M(−1). The enthalpy and entropy changes (∆H(0) and ∆S(0)) were − 33.09 kJ mol(−1) and 61.78 J mol(−1) K(−1), respectively, showing that hydrophobic and hydrogen bonds constitute the primary binding forces. As indicated by the molecular docking results, palbociclib fits into the AT-rich region of the B-DNA minor groove with four base pairs long binding site. The dynamic performance and stability of the formed complex were also evaluated using molecular dynamic simulation studies. The in vitro study of the intermolecular binding interaction of palbociclib with calf thymus DNA could guide future clinical and pharmacological studies for the rational drug scheming with enhanced or more selective activity and greater efficacy.
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spelling pubmed-94277882022-09-01 Multi-spectroscopic, thermodynamic, and molecular docking/dynamic approaches for characterization of the binding interaction between calf thymus DNA and palbociclib Magdy, Galal Shaldam, Moataz A. Belal, Fathalla Elmansi, Heba Sci Rep Article Studying the binding interaction between biological macromolecules and small molecules has formed the core of different research aspects. The interaction of palbociclib with calf thymus DNA at simulated physiological conditions (pH 7.4) was studied using different approaches, including spectrophotometry, spectrofluorimetry, FT-IR spectroscopy, viscosity measurements, ionic strength measurements, thermodynamic, molecular dynamic simulation, and docking studies. The obtained findings showed an apparent binding interaction between palbociclib and calf thymus DNA. Groove binding mode was confirmed from the findings of competitive binding studies with ethidium bromide or rhodamine B, UV–Vis spectrophotometry, and viscosity assessment. The binding constant (K(b)) at 298 K calculated from the Benesi–Hildebrand equation was found to be 6.42 × 10(3) M(−1). The enthalpy and entropy changes (∆H(0) and ∆S(0)) were − 33.09 kJ mol(−1) and 61.78 J mol(−1) K(−1), respectively, showing that hydrophobic and hydrogen bonds constitute the primary binding forces. As indicated by the molecular docking results, palbociclib fits into the AT-rich region of the B-DNA minor groove with four base pairs long binding site. The dynamic performance and stability of the formed complex were also evaluated using molecular dynamic simulation studies. The in vitro study of the intermolecular binding interaction of palbociclib with calf thymus DNA could guide future clinical and pharmacological studies for the rational drug scheming with enhanced or more selective activity and greater efficacy. Nature Publishing Group UK 2022-08-30 /pmc/articles/PMC9427788/ /pubmed/36042232 http://dx.doi.org/10.1038/s41598-022-19015-9 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Magdy, Galal
Shaldam, Moataz A.
Belal, Fathalla
Elmansi, Heba
Multi-spectroscopic, thermodynamic, and molecular docking/dynamic approaches for characterization of the binding interaction between calf thymus DNA and palbociclib
title Multi-spectroscopic, thermodynamic, and molecular docking/dynamic approaches for characterization of the binding interaction between calf thymus DNA and palbociclib
title_full Multi-spectroscopic, thermodynamic, and molecular docking/dynamic approaches for characterization of the binding interaction between calf thymus DNA and palbociclib
title_fullStr Multi-spectroscopic, thermodynamic, and molecular docking/dynamic approaches for characterization of the binding interaction between calf thymus DNA and palbociclib
title_full_unstemmed Multi-spectroscopic, thermodynamic, and molecular docking/dynamic approaches for characterization of the binding interaction between calf thymus DNA and palbociclib
title_short Multi-spectroscopic, thermodynamic, and molecular docking/dynamic approaches for characterization of the binding interaction between calf thymus DNA and palbociclib
title_sort multi-spectroscopic, thermodynamic, and molecular docking/dynamic approaches for characterization of the binding interaction between calf thymus dna and palbociclib
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9427788/
https://www.ncbi.nlm.nih.gov/pubmed/36042232
http://dx.doi.org/10.1038/s41598-022-19015-9
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